Devices, systems, and methods for training pelvic floor muscles

ABSTRACT

Featured are intravaginal devices and methods of using the devices to observe the state of an individual&#39;s pelvic floor muscles in order to diagnose, treat, or prevent pelvic floor disorders (e.g., pelvic organ prolapse and incontinence) and their accompanying symptoms and methods of using the devices to treat or prevent vaginal disorders (e.g., skin laxity) in a subject using an energy transmitter (e.g., a radiofrequency transmitter). Also featured are algorithms to detect pelvic floor movements and physiological indicia from sensor data.

BACKGROUND

Pelvic floor disorders (PFDs) are a group of conditions that occurpredominantly in women and that are associated with weakened (e.g.,hypotonic) or tense (e.g., hypertonic) pelvic floor (PF) muscles. Manycommon factors contribute to the weakening or tightening of the pelvicfloor muscles in women, such as, for example, pregnancy, vaginalchildbirth, pelvic surgery, aging, genetic predisposition, neurologicaldisease, and weight gain. In the United States, PFDs occur in 24% ofwomen, with 16% of women experiencing urinary incontinence (UI), 3%experiencing pelvic organ prolapse (POP), and 9% experiencing anal orfecal incontinence (FI). The prevalence of PFDs increases with age, suchthat 10% of women aged 20-39 and 50% of women aged 80 years or olderwill experience at least one PFD. The number of women in the UnitedStates having at least one PFD is estimated to increase from 28.1million in 2010 to 43.8 million in 2050 (Memon et al., Womens Health(Lond. Engl.). 9(3), 2013).

There exists a need for methods and devices for diagnosing, monitoring,and treating PFDs.

SUMMARY OF THE INVENTION

In a first aspect, featured is a method of detecting a pelvic floormovement in a subject wearing an intravaginal device including one ormore sensors including:

a) obtaining positional data from the one or more sensors;b) processing the data from the one or more sensors to determine anoccurrence of the pelvic floor movement; andc) employing the processed data to provide an alert presentingphysiological data regarding the pelvic floor movement.

In a second aspect, featured is a method of training an intravaginaldevice including one or more sensors including:

a) obtaining positional data from the one or more sensors duringperformance of one or more pelvic floor movements by a subject wearingthe intravaginal device; andb) processing the data from the one or more sensors to establish abaseline for identifying an occurrence of an event (e.g., pelvic floormovement).

During the method of the first or second aspect, the method involveshaving the subject perform one or more than one pelvic floor movement(e.g., a pelvic floor lift, a pelvic floor hold, and a Valsalvamaneuver). The positional data may include one or both of sensor angleand time. Processing the data may include using an algorithm tocalculate one or more composite scores. The one or more composite scoresmay be calculated from the angle of the one or more sensors. Thecomposite score may be a sum of the angle of the one or more sensors.

The methods described herein may further include calculating a movingaverage of the composite score to filter noise. The methods may furtherinclude calculating a change in sensor angle with respect to time. Themethods may further include calculating a derivative of the change insensor angle with respect to time. When the change in sensor angle withrespect to time exceeds a predetermined threshold (e.g., 5°/sec,10°/sec, 15°/sec, 20°/sec, 25°/sec, 30°/sec, or more, or a threshold inthe range of from 5°/sec-30°/sec), the pelvic floor movement may bedetected. A peak of the moving average may be defined as a maximumcomposite score. An end of the pelvic floor movement may be determinedwhen the moving average drops below a predetermined threshold. Thepredetermined threshold may be proportional to the maximum compositescore. The derivative of the change in sensor angle with respect to timemay be used to detect the start or finish of a pelvic floor movement(e.g., when the derivative of the change in sensor angle with respect totime is equal to zero).

In any of the above embodiments, the intravaginal device may include aplurality of sensors (e.g., the sensors may be MEMS accelerometers),which may be located along a length of the device (e.g., equally spacedalong a length of the device or variably spaced).

The methods described herein may further include optimizing thealgorithm for determining the occurrence of a pelvic floor movement (orother event) by measuring a change in sensor angle for each of thesensors, in which the change in sensor angle is the difference betweenan angle during a pelvic floor lift and an angle during pelvic floorrelaxation. The methods may further include calculating the compositescore by using a weighted sum of each of the plurality of sensor angles.

The methods may further include determining physiological indicia fromone or more additional sensors (e.g., a gyroscope, a magnetometer, abarometer, a relative humidity sensor, a bioimpedance sensor, athermometer, a biopotential sensor, a photoplethysmography sensor, andan optical sensor). The physiological indicia may be selected fromsteps, gait, activity, ballistocardiography, heart rate, heart ratevolume, relative stroke volume, respiration rate, rotation, balance,pressure, relative humidity, body composition, temperature, pulsetransit time, pulse oxygenation, and blood pressure. The physiologicalindicia may be indicative of a disease or condition (e.g., when thephysiological indicia exceed or drop below a predetermined threshold).The intravaginal device, peripheral device, or user interface may alertthe subject or another person (e.g., a health care provider) upondetection of a disease or condition.

In a third aspect, featured is a peripheral device comprising a computerprocessing unit configured to receive data from one or more sensors inan intravaginal device, in which the peripheral device is configured toprocess the data collected from the one or more sensors (e.g., MEMSaccelerometers) to establish a baseline for identifying an occurrence ofa predetermined event (e.g., a pelvic floor movement (e.g., pelvic floorlift, pelvic floor relaxation, Valsalva maneuver, sustained pelvic floorlift, and serially repeated pelvic floor lift) or an event related tophysiological indicia related to steps, gait, activity,ballistocardiography, heart rate, heart rate volume, relative strokevolume, respiration rate, rotation, balance, pressure, relativehumidity, body composition, temperature, pulse transit time, pulseoxygenation, and blood pressure). The processing step may include usingan algorithm that identifies a pelvic floor movement. The positionaldata may include one or both of sensor angle and time. Processing thedata may include using an algorithm to calculate one or more compositescores. The one or more composite scores may be calculated from theangle of the one or more sensors. The composite score may be a sum ofthe one or more sensor angles.

The peripheral device described herein may further calculate a movingaverage of the composite score to filter noise. The peripheral devicemay further calculate a change in sensor angle with respect to time. Theperipheral device may further calculate a derivative of the change insensor angle with respect to time. When the change in sensor angle withrespect to time exceeds a predetermined threshold (e.g., 5°/sec,10°/sec, 15°/sec, 20°/sec, 25°/sec, 30°/sec, or more, or a threshold inthe range of from 5°/sec-30°/sec), the pelvic floor movement may bedetected. A peak of the moving average may be defined as a maximumcomposite score. An end of the pelvic floor movement may be determinedwhen the moving average drops below a predetermined threshold. Thepredetermined threshold may be proportional to the maximum compositescore. The derivative of the change in sensor angle with respect to timemay be used to detect the start or finish of a pelvic floor movement(e.g., when the derivative of the change in sensor angle with respect totime is equal to zero). The peripheral device may be configured to allowtransfer and analysis of the baseline measurements through one or moreprocesses or mechanisms that enables operation of the intravaginaldevice to be personalized for a given user.

In a fourth aspect, featured is a system including the peripheral deviceof any one of the above embodiments and the intravaginal deviceincluding the one or more sensors (e.g., as described in any of theabove aspects). The intravaginal device may have a plurality of sensors(e.g., MEMS accelerometers) located along a length of the device (e.g.,equally spaced along a length of the device or variably spaced). Theintravaginal device may further include one or more additional sensors(e.g., a gyroscope, a magnetometer, a barometers, a relative humiditysensor, a bioimpedance sensor, a thermometer, a biopotential sensor, aphotoplethysmography sensor, and an optical sensor). The one or moreadditional sensors may be configured to measure physiological indiciaselected from steps, gait, activity, ballistocardiography, heart rate,heart rate volume, relative stroke volume, respiration rate, rotation,balance, pressure, relative humidity, body composition, temperature,pulse transit time, pulse oxygenation, and blood pressure.

In another aspect, the invention features an intravaginal devicecomprising a main body having an outer edge configured to contact avaginal wall (e.g., in proximity to the cervix) or a vaginal fornix andan internal diameter sized to encircle a cervix or vaginal cuff and atether connected to the main body and comprising one or moremotion-detecting sensors (e.g., pelvic floor muscle movement) located onthe tether at a distance of 7 cm or less from the main body.

In another aspect, the invention features an intravaginal devicecomprising a main body having an outer edge configured to contact avaginal wall (e.g., in proximity to the cervix) or vaginal fornix and aninternal diameter sized to encircle a cervix or vaginal cuff, a tetherconnected to the main body and comprising one or more motion-detectingsensors (e.g., sensors for detecting pelvic floor muscle movement)located on the tether; and/or one or more energy transmitters (e.g.,radio frequency (RF) energy transmitters, lasers, or electricalstimulators). The one or more motion-detecting sensors and/or the one ormore energy transmitters (e.g., RF transmitters) may be located on thetether at a distance of 7 cm or less from the main body.

In another aspect, the invention features an intravaginal devicecomprising a main body having an outer edge configured to contact avaginal wall or vaginal fornix and an internal diameter sized toencircle a cervix or vaginal cuff and a tether connected to the mainbody and comprising one or energy transmitters located on the tether.The intravaginal device may further comprise one or moremotion-detecting sensors, optionally wherein the one or moremotion-detecting sensors are located on the tether at a distance of 7 cmor less from the main body.

In another aspect, the invention features an intravaginal devicecomprising a main body having an outer edge configured to contact avaginal wall or vaginal fornix and an internal diameter sized toencircle a cervix or vaginal cuff and a tether connected to the mainbody and comprising one or more motion-detecting sensors and/or one ormore energy transmitters (e.g., RF transmitter, lasers, or electricalstimulators) located on the tether. The tether can be configured to haveone or more separable pieces. The separable piece(s) of the tether maybe joined by a magnetic or interlocking connection. The separablepiece(s) of the tether may contain an electrical connection at ajunction there-between. One of the pieces may be connected to anexternal power source. The external power source may provide an amountof energy to the separable piece(s) of the tether, the tether connectedto the main body, and/or to the main body (e.g., 1 mW-500 W, e.g., 100mW-300 W, e.g., 1-10 mW, e.g., 2 mW, 3 mW, 4 mW, 5 mW, 6 mW, 7 mW, 8 mW,9 mW, 10 mW, e.g., 10-100 mW, e.g., 20 mW, 30 mW, 40 mW, 50 mW, 60 mW,70 mW, 80 mW, 90 mW, 100 mW, e.g., 100-1000 mW, e.g., 200 mW, 300 mW,400 mW, 500 mW, 600 mW, 700 mW, 800 mW, 900 mW, 1 W, e.g., 1-10 W, e.g.,2 W, 3 W, 4 W, 5 W, 6 W, 7 W, 8 W, 9 W, 10 W, e.g., 10-100 W, e.g., 20W, 30 W, 40 W, 50 W, 60 W, 70 W, 80 W, 90 W, 100 W, e.g., 100-1000 W,e.g., 200 W, 300 W, 400 W, 500 W, 600 W, 700 W, 800 W, 900 W, 1000 W).The energy is sufficient to power a component or sensor of the device(e.g., one or more of the sensors, an RF energy transmitter, or laser).The RF transmitter may operate at a frequency of 1 kHz to 100 MHz (e.g.,1 kHz to 50 MHz, e.g., 1-10 kHz, e.g., 1 kHz, 2 kHz, 3 kHz, 4 kHz, 5kHz, 6 kHz, 7 kHz, 8 kHz, 9 kHz, 10 kHz, 10-100 kHz, e.g., 20 kHz, 30kHz, 40 kHz, 50 kHz, 60 kHz, 70 kHz, 80 kHz, 90 kHz, 100 kHz, e.g.,100-1 MHz, e.g., 200 kHz, 300 kHz, 400 kHz, 500 kHz, 600 kHz, 700 kHz,800 kHz, 900 kHz, 1 MHz, e.g., 1-10 MHz, e.g., 2 MHz, 3 MHz, 4 MHz, 5MHz, 6 MHz, 7 MHz, 8 MHz, 9 MHz, 10 MHz, e.g., 10-100 MHz, e.g., 20 MHz,30 MHz, 40 MHz, 50 MHz, 60 MHz, 70 MHz, 80 MHz, 90 MHz, 100 MHz).

The intravaginal device may be configured such that the sum of thevaginal angle and fornix angle ranges from about 30° to about 120°. Thevaginal angle may be defined as an angle formed by a line drawn betweenthe position of at least two of the sensors in the tether and thehorizon. In some embodiments, the main body may comprise at least one(e.g., 2, 3, 4, and 5) pair of sensors anteriorly and one sensorposteriorly such that an angle formed by a line connecting the averagedlocation of the at least one (e.g., 2, 3, 4, and 5) pair of sensorsanteriorly and the posterior sensor and by a line parallel to thehorizon defines a fornix angle. In some embodiments the main bodycomprises at least four unpaired sensors, and the angle formed by theline connecting at least two of the sensors and a line parallel to thehorizon defines the fornix angle.

The intravaginal device may be made from a flexible, biocompatiblematerial (e.g., silicone, polyethylene, polypropylene, polystyrene,polyester, polycarbonate, polyvinyl chloride, polyethersulfone,polyacrylate, hydrogel, polysulfone, polyetheretherketone, thermoplasticelastomers, poly-p-xylylene, fluoropolymers, rubber, and latex).

The intravaginal device may be configured for use with a tool forinsertion. The tool for insertion may be capable of deforming theintravaginal device and/or deploying the intravaginal device within thevagina of the individual so that the main body encircles the cervix orvaginal cuff and the tether extends from the posterior fornix in acaudal direction through the vagina.

In some embodiments of any of the above aspects, the tether may have oneor more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, and 50) of themotion-detecting sensors. The main body may have one or more (e.g., 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, and 50) of the motion-detectingsensors. In some embodiments, the main body has two to ten of themotion-detecting sensors and the tether has five of the motion-detectingsensors. One of the motion-detecting sensors may be shared by the mainbody and the tether. The intravaginal device may be used to detect apelvic floor muscle movement (e.g., pelvic floor lift, pelvic floorrelaxation, Valsalva maneuver, sustained pelvic floor lift, and seriallyrepeated pelvic floor lift).

In some embodiments of any of the above aspects, the main body may havea complete or incomplete circular form (e.g., a horseshoe form) or itmay have a cup-shaped form. The main body or tether may further have amicrocontroller for receiving and storing data from the one or moresensors. The main body or tether may further comprise a wiredtransmitter and/or receiver for communicating (e.g., wirelessly) data toan electronic device (e.g., computer, tablet, smartphone, and smartwatch). The intravaginal device may be configured to send data to andreceive data from the electronic device. The transmitter and/or receivermay be configured for use with a Bluetooth and/or Wi-Fi enabledelectronic device. The transmitter and/or receiver may be located in anexternal housing connected to the intravaginal device by a detachablecable, which may be configured to assist in the removal of theintravaginal device. The electronic device may comprise a display (e.g.,graphical user interface and/or a touch user interface). The RFtransmitter, laser, and/or other sensors may be controllable viaBluetooth or Wi-Fi.

In some embodiments of any of the above aspects, the intravaginal devicemay comprise a power source (e.g., battery) connected to the one or moresensors. The sensors may be one or more of an accelerometer (e.g.,multiple-axis accelerometer), gyroscope (e.g., multiple-axis gyroscope),micro-electro-mechanical systems (MEMS) sensor, G-sensor, tilt sensor,rotation sensor, a light detecting sensor, such as a light detecting andranging (LiDAR) sensor, and/or an electrical impedance myography (EIM)sensor (e.g., localized biological transfer impedance (LBTI) sensor).The intravaginal device may comprise a combination of sensors ofdiffering types and/or may further comprise at least one additionalsensor within the main body selected from the group consisting of apressure sensor, a muscle quality sensor, a muscle strength sensor, a pHsensor, a humidity sensor, a temperature sensor, a hormone sensor, and atoxin sensor.

In some embodiments, the length of the tether is about 3 cm to about 50cm (e.g., 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50 cm, e.g., 25.5 cm).In some embodiments, the circumference of the main body is about 10 cmto about 50 cm (e.g., 10, 15, 20, 25, 30, 35, 40, 45, and 50 cm, e.g.,27 cm). In certain specific embodiments, the intravaginal devicecomprises two or more (e.g., 3, 4, 5, 6, 7, 8, 9, and 10) sensors on thetether that are separated on the tether by a distance of about 0.5 cm toabout 5 cm (e.g., 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5, e.g., 1.6 cm).

In another aspect, the invention features a system comprising theintravaginal device of any of the above aspects of the invention and agraphical user interface. The graphical user interface may be tetheredwirelessly to the intravaginal device. The system may further comprise atransmitter and receiver, a detachable cable, a tool for insertion ofthe intravaginal device, an electronic device, and/or a database. Thesystem may be used for treating or reducing the progression of a pelvicfloor disorder (e.g., urinary incontinence, stress urinary incontinence,urge incontinence, mixed stress and urge urinary incontinence, anal orfecal incontinence, coital incontinence, pelvic organ prolapse, pelvicpain, sexual dysfunction, weak or impaired pelvic floor muscle function,post-labor issues or damage, pain and/or incontinence caused by damageto a lumbosacral nerve, muscle pain, nonrelaxing pelvic floordysfunction, vaginismus, urethral hypermobility, cystocele, rectocele,and enterocele) in a subject.

In another aspect, the invention features a method of diagnosing apelvic floor disorder, by inserting the intravaginal device of any oneof the above aspects into a subject's (e.g., human) vagina andmonitoring contraction of, or relaxation of, a pelvic floor muscle bydetecting motion of the one or more sensors.

In another aspect, the invention features a method of treating,inhibiting, or reducing the development or progression of a pelvic flooror vaginal disorder in a subject by inserting the intravaginal device ofany of the above aspects into a subject's (e.g., a human's) vagina andmonitoring the contraction of, or relaxation of, a pelvic floor muscleby detecting position or motion of the one or more sensors, in which thetreatment reduces the frequency of occurrence and/or severity of atleast one symptom (e.g., muscle tone, muscle strength, bladder leakage,anal or fecal leakage, pain, frequency, skin laxity, and urgency) of apelvic floor or vaginal disorder.

In another aspect, the invention features a method of treating,inhibiting, or reducing the development or progression of, a pelvicfloor or vaginal disorder in a subject, the method by inserting theintravaginal device of any of the above aspects into a subject's vaginaand transmitting energy from the one or more energy transmitters,wherein the treatment reduces the frequency of occurrence and/orseverity of at least one symptom (e.g., muscle tone, muscle strength,bladder leakage, anal or fecal leakage, pain, frequency, skin laxity,and urgency) of a pelvic floor or vaginal disorder. Exemplary vaginaldisorders are vaginal laxity, pelvic organ prolapse, incontinence,tissue tone (e.g., moisture and tightness), nerve sensitivity, orgasmicdysfunction, vulvovaginal laxity (e.g., in labial and vaginal tissues),atrophic vaginitis, stress incontinence, and pubocervical fasciatightening. The one or more energy transmitters may be radio frequencytransmitters, which are used to heat vaginal tissue. The method may beperformed for 1-30 minutes (e.g., 10, 15, 20, or 25 minutes) or more persession. The sessions may be repeated one or more times per for one ormore days (e.g., 1 week, 1 month, 6 months, 1 year, or more). Theintravaginal device may be recharged after a use or several uses. Theenergy transmitters may transmit energy (e.g., 1 mW-500 W, e.g., 100mW-300 W, e.g., 1-10 mW, e.g., 2 mW, 3 mW, 4 mW, 5 mW, 6 mW, 7 mW, 8 mW,9 mW, 10 mW, e.g., 10-100 mW, e.g., 20 mW, 30 mW, 40 mW, 50 mW, 60 mW,70 mW, 80 mW, 90 mW, 100 mW, e.g., 100-1000 mW, e.g., 200 mW, 300 mW,400 mW, 500 mW, 600 mW, 700 mW, 800 mW, 900 mW, 1 W, e.g., 1-10 W, e.g.,2 W, 3 W, 4 W, 5 W, 6 W, 7 W, 8 W, 9 W, 10 W, e.g., 10-100 W, e.g., 20W, 30 W, 40 W, 50 W, 60 W, 70 W, 80 W, 90 W, 100 W, e.g., 100-1000 W,e.g., 200 W, 300 W, 400 W, 500 W, 600 W, 700 W, 800 W, 900 W, or 1000W), e.g., in units of energy per area (e.g., 1 mm² to 10 cm², e.g., 1-10mm², 10-100 mm², or 1-10 cm²) and, e.g., for a set amount of time (e.g.,10 seconds-30 minutes or more, e.g., 30 seconds, 1 minute, 10 minutes,20 minutes, or 30 minutes). The energy may also be transmitted to acertain depth within the tissue (e.g., 0.1 mm-10 cm, e.g., 1 mm, 2 mm, 3mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 20 mm, 30 mm, 40 mm, 50mm, 60 mm, 70 mm, 80 mm, 90 mm, 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7cm, 8 cm, 9 cm, 10 cm).

The subject may be standing or lying down during performance of themethods of the above aspects.

Any of the above methods may include measuring a vaginal angle formed bya line between a position of at least two of the sensors in the tetherand a line parallel to a horizon. In some embodiments, the methodinvolves using an intravaginal device with a tether having eight of themotion-detecting sensors, and in which the vaginal angle is formed by aline between the position of at least two of the sensors in the tetherand a line parallel to the horizon. The vaginal angle may be measuredduring PFR, Valsalva maneuver, and/or PFL. The method may comprisedetermining whether the vaginal angle increases above or decreases belowa predetermined threshold (e.g., a vaginal angle determined at rest orin the subject at a prior time). The method may include diagnosing thesubject with a pelvic floor disorder when the vaginal angle increasesabove or decreases below a predetermined threshold during a pelvic floormovement.

The method may include measuring a fornix angle by detecting a positionof at least two of the one or more sensors in the main body, wherein anangle formed by a line connecting an averaged location of each pair ofthe sensors in the anterior and mid-main body and a line parallel to thehorizon defines a fornix angle. In some embodiments, the main body hasfive of motion-detecting sensors and an angle formed by the lineconnecting an averaged location of two pairs of sensors (e.g., a pair ofsensors in the anterior main body and a pair of sensors in the mid-mainbody) and a line parallel to the horizon defines a fornix angle. Themethod may include measuring the fornix angle during PFR, Valsalvamaneuver, and/or PFL.

In some embodiments of any of the above methods, the tether has at leastthree of the motion-detecting sensors, and a level of curvature of aspatial orientation of the at least three sensors increases above ordecreases below a predetermined threshold. The method may comprisediagnosing the subject with a pelvic floor disorder when the level ofcurvature increases above or decreases below a predetermined threshold(e.g., a level of curvature determined in the subject at rest or in thesubject at a prior time).

The method may further comprise displaying a graphical representation ofthe position of the one or more sensors and/or the device on a graphicaluser interface. The vaginal angle or fornix angle may be displayed onthe graphical user interface.

The method may further comprise measuring a performance metric (e.g.,execution of PFL or PFR) as measured by the one or more sensors. Theperformance metric may be a duration of time during which theintravaginal device is in use. The performance metric may be selectedfrom a measurement of pressure, muscle quality, muscle strength,humidity, temperature, a hormone level, a toxin level, and/or pH. Thepelvic floor disorder may be urinary incontinence, stress urinaryincontinence, urge incontinence, mixed stress and urge urinaryincontinence, anal or fecal incontinence, coital incontinence, pelvicorgan prolapse, pelvic pain, sexual dysfunction, weak or impaired pelvicfloor muscle function, post-labor disorder or damage, pain and/orincontinence caused by damage to a lumbosacral nerve, muscle pain,nonrelaxing pelvic floor dysfunction, vaginismus, urethralhypermobility, cystocele, rectocele, and/or enterocele.

In some embodiments of any of the above aspects, the inner diameter ofthe main body of the intravaginal device is positioned around the cervixor vaginal cuff and the external diameter of the main body is positionedin the vaginal fornix. The one or more sensors on the tether may belocated approximately halfway between an introitus of the vagina and thecervix, vaginal cuff, or vaginal fornix.

Definitions

As used herein, the singular form “a,” “an,” and “the” includes pluralreferences unless indicated otherwise.

As used herein, the terms “about” and “approximately” mean +/−10% of therecited value.

As used herein, “administering” is meant a method of giving a dosage(e.g., a pharmaceutically effective dosage) of a pharmaceutical agent(e.g., a pharmaceutical agent useful in the treatment of a pelvic floordisorder (PFD) or a symptom thereof) to a subject. The pharmaceuticalagents and compositions utilized in the methods described herein can beadministered, e.g., by an intravaginal device of the invention. Theintravaginal device may be configured to contain at least onepharmaceutical agent (e.g., 1, 2, 3, 4, 5, or more pharmaceuticalagents). For example, the pharmaceutical agent may be uniformlydispersed or dissolved throughout a material (e.g., a polymericmaterial) of the intravaginal device, contained within a delivery module(e.g., an inner core or reservoir incorporated into the intravaginaldevice), and/or contained within a coating, layer, or gel applied to thesurface of the intravaginal device. The amount of an agent administeredby, e.g., an intravaginal device of the invention, can vary depending onvarious factors (e.g., the pharmaceutical agent or composition beingadministered and the severity of the PFD, or the symptom thereof, beingtreated). The intravaginal device can be configured to control the rateof pharmaceutical agent release (e.g., continuous release, periodicrelease, or release in response to, e.g., user input, a stimuli, and/orsensor data obtained by the intravaginal device) and/or to enable thedelivery (e.g., simultaneous and/or consecutive delivery) of more thanone pharmaceutical agent (e.g., 1, 2, 3, 4, 5, or more pharmaceuticalagents).

As used herein, the phrase “approximately circumferentially surround acervix or a vaginal cuff” refers to the form of an intravaginal device,such that the form is capable of encircling and/or cupping the cervix orvaginal cuff.

As used herein, the term “in proximity to” and “proximal” refers to alocation near (e.g., about 0.01-5 mm from, or adjacent to, the tissuesurface surrounding the cervix or vaginal cuff) the tissues of thevagina surrounding the cervix or vaginal cuff of a subject at which anintravaginal device of the invention is positioned during treatment(e.g., performance of pelvic floor lifts (PFLs) and/or pelvic floorrelaxations (PLRs)).

As used herein, the term “biofeedback” refers to information that can beused to train an individual to change physiological activity (e.g.,pelvic floor muscle function) for the purpose of improving health andperformance (e.g., treating, reducing, and/or preventing the occurrenceof or the symptoms of a pelvic floor disorder (PFD)). Biofeedback mayalso include information collected by an intravaginal device of theinvention during daily monitoring, e.g., in substantially real-time,while a user performs her daily activities. The information can bereviewed substantially in real-time or can be accessed for review at alater time. Instruments, such as an intravaginal device of the inventioncan be used to measure physiological activity, such as muscle activity(e.g., movement and pressure), vaginal pressure, muscle quality, andvaginal canal pH, temperature, and humidity, and to provide thisinformation as biofeedback to the individual. Instruments, such as anintravaginal device of the invention can also be used to measure thelevel of a molecule, e.g., the level of a hormone and/or the level of atoxin, and to provide this information as biofeedback to the individual.The presentation of this information to the individual can be by avisual, audible, or tactile signal, and can support a desiredphysiological change (e.g., improved pelvic floor muscle strength,control, and quality).

As used herein, the term “biocompatible material” refers to materialsthat are not harmful or toxic to living tissues.

As used herein, the term “calibration period” refers to the process ofdetermining a baseline set of measurements from the sensors positionedwithin the intravaginal device during a period of use of theintravaginal device by an individual, such that the baseline set ofmeasurements characterize the health (e.g., strength, muscle quality,condition) of the individual's pelvic floor muscles prior to or at thestart of a treatment program. The baseline set of measurements collectedduring the calibration period can be used to calculate and/or determinethe progress of an individual through a treatment program.

As used herein, the term “continence” is defined as the ability torefrain from or to retain a bodily discharge (e.g., urination,defecation, or passage of flatus).

As used herein, the term “detection” means the action or process ofidentifying information, e.g., the activation and/or the relaxation of apelvic floor muscle. Detection can occur from a direct or indirectsource (e.g., a sensor).

As used herein, “delaying progression” of a disorder or disease means todefer, hinder, slow, retard, stabilize, and/or postpone development ofthe disease or disorder (e.g., a pelvic floor disorder (PFD)). Thisdelay can be of varying lengths of time, depending on the history of thedisease and/or individual being treated. As is evident to one skilled inthe art, a sufficient or significant delay can, in effect, encompassprevention, in that the individual does not develop the disease ordisorder. For example, a PFD after vaginal childbirth may be delayedand/or prevented.

As used herein, the term “diagnosis” refers to the identification orclassification of a disease or condition (e.g., a pelvic floordisorder). For example, “diagnosis” may refer to identification of aparticular type of PFD.

A “disorder” is any condition that would benefit from treatmentincluding, but not limited to, chronic and acute disorders or diseasesincluding those pathological conditions which predispose the subject tothe disorder in question.

As used herein, the term “monitoring” refers to a use of an intravaginaldevice of the invention to collect, track, and/or store data, e.g., dataobtained from sensor(s) of the intravaginal device, as described herein.The monitoring occurs, e.g., when the intravaginal device is positionedwithin the vaginal cavity of a user and/or when the intravaginal deviceis used during a treatment period (e.g., during the performance of aseries of pelvic floor exercise (e.g., a pelvic floor lift and/orrelaxation)). The monitoring may also occur, e.g., substantially inreal-time while a user performs her daily activities. This featureallows the user, effectively in real-time, to alter activities orbehaviors that cause pelvic floor damage or to continue activities orbehaviors that improve pelvic floor health. Alternatively, data storedby the device during monitoring can be accessed by the user at a latertime (e.g., 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6hours, 12 hours, 24 hours, or more after activities monitored by thedevice) for analysis of whether the activity or behavior had a positiveor negative effect on pelvic floor health. The process of monitoring caninclude obtaining sensor data (e.g., measurements) that can be used todescribe an individual's pelvic floor muscle movement, pressure,strength, and/or quality. Additionally, vaginal conditions including,but not limited to, shape, size, temperature, pH, and/or moisture levelmay also be monitored by an intravaginal device of the invention. Anintravaginal device of the invention may also be configured to detectthe level of a molecule, e.g., the level of a hormone and/or the levelof a toxin.

As used herein, the terms “pelvic floor lift” and “PFL” refers to amovement of the pelvic floor (e.g., the muscle fibers of the levator ani(e.g., the pubococcygeus, ileococcygeus, coccygeus, and puborectalismuscles) and the associated connective tissues which span the area in aspherical form from the pubic bone anteriorly to the sacrum posteriorlyand to the adjoining bony structure joining these two bones, which ischaracterized by an upward movement (e.g., a lifting movement, such as amovement in the cranial direction) of the pelvic floor. The movement ofthe pelvic floor during the performance of a PFL is adistinctly-described component of the collective action of the entirepelvic floor (e.g., the levator ani, urethral and anal sphincters,bulbocavernosus, ischiocavernosus, superficial tranverse perinealmuscles) whereby the combined lifting and circumferentially-directedsqueezing action is produced when all muscles are activatedsimultaneously. A PFL is a type of pelvic floor muscle training (PFMT)exercise that selectively targets the levator ani component of thepelvic floor.

As used herein, the terms “pelvic floor relaxation” and “PFR” refers toa movement of the pelvic floor (e.g., the muscle fibers of the levatorani (e.g., the pubococcygeus, ileococcygeus, coccygeus, and puborectalismuscles) and the associated connective tissues which span the area in aspherical form from the pubic bone anteriorly to the sacrum posteriorlyand to the adjoining bony structure joining these two bones), which ischaracterized by a relaxation (e.g., a downward movement, such as amovement in the caudal direction) of the pelvic floor. The movement ofthe pelvic floor during the performance of a PFR is distinct from theconcentric contraction (e.g., shortening contraction) of the PFL, andrepresents the lengthening or relaxation of the muscle fibers. A PFR isa type of PFMT exercise.

As used herein, the term “pharmaceutically acceptable” as applied to apharmaceutical agent, such as a compound, material, composition and/ordosage form, means that the agent is suitable for contact with vaginaltissues of an individual, e.g., without causing excessive toxicity,irritation, allergic response, or other complications. A determinationof “pharmaceutically acceptable” can be made using, e.g.,industry-recognized and/or Food and Drug Administration (FDA)-recognizedstandards.

By “pharmaceutically acceptable diluent, excipient, carrier, oradjuvant” is meant a diluent, excipient, carrier, or adjuvant that isphysiologically acceptable to a subject while retaining the therapeuticproperties of the pharmaceutical composition with which it isadministered. One exemplary pharmaceutically acceptable carrier isphysiological saline. Other physiologically acceptable diluents,excipients, carriers, or adjuvants and their formulations are known toone skilled in the art and described, for example, in Remington'sPharmaceutical Sciences (18th edition, A. Gennaro, 1990, Mack PublishingCompany, Easton, Pa.), incorporated herein by reference.

As used herein, the term “pharmaceutical composition” refers to amedicinal or pharmaceutical formulation or adjuvant that contains anactive ingredient (e.g., a pharmaceutical agent) and may contain one ormore excipients, carriers, or diluents. The pharmaceutical compositionmay include a pharmaceutically acceptable component that is compatiblewith intravaginal delivery, e.g., by an intravaginal device of theinvention. The pharmaceutical composition may be, e.g., in solid orliquid form. To facilitate controlled-release from an intravaginaldevice of the invention, a pharmaceutical composition may also beformulated to be, e.g., time-released and/or to release upon exposure toan environmental condition, such as a pre-determined temperature,moisture level, and/or pH. Exposure to such an environmental conditionmay, e.g., dissolve a drug-impervious coating around the pharmaceuticalagent and/or increase the solubility of the pharmaceutical agent invaginal fluid.

As used herein, the term “pharmaceutically effective,” refers to anamount of a pharmaceutical agent that is sufficient to produce a desiredphysiological or pharmacological change in a subject. This amount mayvary depending upon such factors as the potency of the particularpharmaceutical agent, the desired physiological or pharmacologicaleffect, and the time span of the intended treatment. Those skilled inthe pharmaceutical arts will be able to determine the pharmaceuticallyeffective amount for any given pharmaceutical agent in accordance withstandard procedures.

As used herein, “real-time” refers to the actual time during which anevent, such as a daily activity, occurs.

As used herein, “sensor data” refers to measurements (e.g., any one ormore of measurements of pelvic floor muscle movement, pelvic floormuscle quality, pelvic floor muscle strength, pressure, and measurementsof other vaginal conditions, such as pH, temperature, and/or moisture),which characterize an individual's pelvic floor health and are obtainedby a sensor(s), as described herein, of an intravaginal device of theinvention. Sensor data may also be collected that characterize the levelof a molecule, e.g., the level of a hormone and/or the level of a toxin.

As used herein, “radio frequency” refers to electromagnetic waves thathave a frequency in the range from 10³ Hz to 10¹² Hz.

As used herein, a “subject,” “patient,” or “individual” is a human, inparticular, a female.

As used herein, the terms “reducing” and “inhibiting” are defined as theability to cause an overall decrease of about 10%, 20%, 30%, 40%, 50%,60%, 70%, 75%, 80%, 85%, 90%, 95%, or more. Reduce or inhibit can refer,for example, to the symptoms of the pelvic floor disorder (PFD) beingtreated.

As used herein, the term “transdermal delivery” refers to a route ofadministration, e.g., of a pharmaceutical agent or composition useful inthe treatment of a PFD, or a symptom thereof, across the skin for, e.g.,systemic distribution.

As used herein, the term “transmucosal delivery” refers to a route ofadministration, e.g., of a pharmaceutical agent or composition useful inthe treatment of a PFD, or the symptoms thereof, involving diffusionthrough a mucous membrane, e.g., the tissues of the vagina.

As used herein, the term “treating” refers to performing pelvic floorlifts (PFLs) and/or pelvic floor relaxations (PFRs) in a subject in needthereof for therapeutic purposes (e.g., to treat or reduce thelikelihood of developing a PFD), in particular in conjunction with theuse of a device or method described herein. To “treat disease” or usefor “therapeutic treatment” includes administering treatment to asubject already suffering from a disease to improve or stabilize thesubject's condition. To “prevent” or “reduce likelihood of developing”disease refers to prophylactic treatment of a subject who is not yet illor symptomatic, but who is susceptible to, or otherwise at risk of, aparticular disease, such as a PFD.

As used herein, and as well understood in the art, “treatment” is anapproach for obtaining beneficial or desired results, such as clinicalresults. Beneficial or desired results can include, but are not limitedto, alleviation or amelioration of one or more symptoms or conditions;diminishment of extent of disease, disorder, or condition; stabilization(i.e., not worsening) of a state of disease, disorder, or condition;prevention of spread of disease, disorder, or condition; delay orslowing the progress of the disease, disorder, or condition;amelioration or palliation of the disease, disorder, or condition; andremission (whether partial or total), whether detectable orundetectable. “Palliating” a disease, disorder, or condition means thatthe extent and/or undesirable clinical manifestations of the disease,disorder, or condition are lessened and/or time course of theprogression is slowed or lengthened, as compared to the extent or timecourse in the absence of treatment.

As used herein, “female urogenital system” or “urogenital system” refersto the organ system of the female reproductive system, which includes,e.g., the Bartholin's glands, cervix, clitoris, clitoral frenulum,clitoral glans (glans clitoridis), clitoral hood, fallopian tubes,labia, labia majora, labia minora, frenulum of labia minora, ovaries,skene's gland, uterus, vagina, and vulva; the urinary system, whichincludes, e.g., the kidneys, ureters, bladder, and the urethra; and thesurrounding and supporting nerves and musculature.

As used herein, “vaginal cuff” refers to the sutured tissue at the topof the vaginal canal remaining after removal of the cervix (e.g., duringa hysterectomy).

As used herein, “pelvic organ prolapse” or “POP” refers to the descentof one or more aspects of the vagina and uterus, such as the anteriorvaginal wall, posterior vaginal wall, the uterus (cervix), or the apexof the vagina (vaginal vault or cuff scar after hysterectomy). Thisdescent allows nearby organs to herniate into the vaginal space, whichis commonly referred to as cystocele, rectocele, or enterocele. Pelvicorgan prolapse may be asymptomatic or associated with one or moresymptoms, such as, e.g., pressure with or without a bulge, sexualdysfunction, and disruption of normal lower urinary tract or bowelfunction. Pelvic organ prolapse can be defined using patient-reportedsymptoms or physical examination findings (e.g., vaginal bulgeprotruding to or beyond the hymen). Most women feel symptoms of POP whenthe leading edge reaches 0.5 cm distal to the hymenal ring. As usedherein, “urinary incontinence” refers to the leaking of urine from thebladder. Incontinence can range from leaking just a few drops of urineto complete emptying of the bladder. Urinary incontinence can be dividedinto three main types: stress urinary incontinence (SUI), urgencyurinary incontinence, and mixed incontinence. Stress urinaryincontinence is leaking urine when coughing, laughing, or sneezing.Leaks can also happen when a woman walks, runs, or exercises. Urgencyurinary incontinence is a sudden strong urge to urinate that is hard tostop. Women with this type of urinary incontinence may leak urine on theway to the bathroom. Mixed incontinence combines symptoms of both stressand urgency urinary incontinence.

As used herein, “pelvic floor” refers to the muscular area at the baseof the abdomen attached to the pelvis.

As used herein, “pelvic floor disorders” or “PFDs” refers to disordersaffecting the muscles and tissues that support the pelvic organs. Thesedisorders may result in loss of control of the bladder or bowels or maycause one or more pelvic organs to drop downward, resulting in prolapse.

DESCRIPTION OF THE DRAWINGS

The application file contains at least one drawing executed in color.Copies of this patent or patent application with color drawings will beprovided by the Office upon request and payment of the necessary fee.

FIG. 1 is a schematic drawing showing an intravaginal device 100 thathas a main body 110 (which may have, e.g., a ring form or an incompletering form), insertion tool 600 (applicator and tool for removal), tether10, and transmitter/receiver box 500. Tether 10 may be non-detachablefrom main body 110 or, if detachable from main body 110, is configuredfor easy removal. Intravaginal device 100 contains circuit board 700,either in main body 110 or tether 10, which connects sensor(s) 200(e.g., accelerometers, such as MEMS sensors), battery 800,microcontroller 900, internal transmitter/receiver 1000, data storagecomponent 1100, sensory output component 1200, wireless communicationantennae 1300, authentication chip 1400 (e.g., an Apple productauthentication chip), and ON/OFF switch 1600. Intravaginal device 100may also contain molded wing 300 for the reduction of rotation andslippage of the device within the vaginal canal of the individual.Intravaginal device 100 may also contain energy transmitters 210 (shownas hatched boxes) either on main body 110 or ring 10. Insertion tool 600may also include plunger 605, e.g., for insertion in the vagina, and tab610, which can be used to hold applicator 600 in place as intravaginaldevice 100 is removed. Any of the above components may or may not bepresent on intravaginal device 100 (e.g., energy transmitters 210, suchas RF transmitters are optional).

FIG. 2 is a schematic drawing showing intravaginal device 100 with mainbody 110 and tether 10. Main body 110 contains 5 sensors 200 (e.g.,accelerometers, such as MEMS sensors) and tether 10 contains 8 sensors200. One sensor 200 is shared by both main body 110 and tether 10.

FIGS. 3A-3D are schematic drawings showing a vaginal angle (θ_(V)) and afornix angle (θ_(F)) referenced relative to intravaginal device 100(e.g., when inserted into a vaginal canal of a subject). When positionedin a vaginal canal of a subject, sensor pair 1 of intravaginal device100 shown in FIG. 3A would reside in the anterior fornix, while thesensors of sensor pair 2 each would reside in a lateral fornix. A singleremaining sensor, sensor 3, would reside in the posterior fornix, thislast being also part of the tether. FIG. 3B shows the anterior fornixsensors, labeled A9 and A12, the sensors in the lateral fornices,labeled A10 and A11, and the single posterior fornix sensor, labeled A8,which is shared by main body 110 and tether 10. Sensors exclusively ontether 10 are labeled A1-A7. The vaginal angle (θ_(V)) is defined as theangle between the line of the tether (essentially demarcating the longaxis of the vagina) and the line contained in a plane parallel to thevirtual plane of the introitus, hereafter designated the “horizon.” Thefornix angle (θ_(F)) is defined as the angle between the line connectingthe anterior and posterior fornices (the anterior and posterior pointsof the main body) and the line of the horizon. FIG. 3C shows (1) thateach sensor of the tether may be connected by a best-fit line and (2)the positions of the two sensors in the anterior fornix may be averaged;similarly, the positions of the sensors in the lateral fornices may beaveraged, and a best fit line may be drawn from the posterior fornix tothe anterior fornix. The vaginal angle (θ_(V)) and fornix angle (θ_(F))are shown in both FIGS. 3C and 3D. In FIG. 3D, the points (“nodes”)shown in FIG. 3C are labeled S1-S10. The sensors depicted are, e.g.,accelerometers, such as MEMS sensors.

FIG. 4 is a schematic drawing showing insertion of intravaginal device100 with main body 110 into the vaginal canal and fornices. Thebidirectional arrow indicates a portion of the device that is outside ofthe introitus. Intravaginal device 100 may be configured to exclude thisexternal portion, such that intravaginal device 100 resides completelywithin the vagina. The length of the vagina can be determined bymeasuring the length of intravaginal device from main body 110 to theend of tether 10 at the point that extends to the introitus.

FIGS. 5A-5B are schematic drawings showing how a visual representationof the physical shape and motion of the intravaginal device can beanalyzed for display on, e.g., a graphical user interface, by measuringthe angles of each sensor in combination with the known spacing betweensensors. FIG. 5A shows the angles and spacing between each sensor in anintravaginal device, while FIG. 5B shows the recreated visualrepresentation provided by a processing device based on the sensor data.

FIGS. 5C-5E are schematic representations of how accelerometers measureangle and position based on the effect of gravity. FIG. 5C shows a3-axis accelerometer, FIG. 5D shows a 2-axis accelerometer, and FIG. 5Eshows a rotated 2-axis accelerometer.

FIGS. 6A-6C are schematic drawings showing changes in the angle of anaccelerometer of an intravaginal device during engagement of pelvicfloor muscles. FIG. 6A shows the angle at rest before a pelvic floorlift, FIG. 6B shows an increase in the angle during a pelvic floor lift,and FIG. 6C shows an overlay of the angle of FIG. 6A on top of therecreated visual representation of the intravaginal device powered by aprocessing device.

FIG. 7 shows two panel images illustrating the positions of sensorsS1-S10 (see, e.g., FIG. 3D) of an intravaginal device in a subject in arelaxed state (left panel) and during a pelvic floor lift (right panel)as recorded by a processing device based on accelerometer sensor data.The bottom dashed line indicates the position of the virtual plane ofthe introitus during each maneuver. The two dashed lines in the upperportion illustrate the position of the posterior fornix sensor duringeach maneuver. During a pelvic floor lift, the posterior fornix sensormoves up 0.8 cm relative to its position during relaxation. The sensordata were generated using MEMS sensors. The upward motion of each sensorcan be quantified as the length of each segment and the angle of eachsensor is known. The upward motion of each sensor can then be used tocalculate the upward motion of the pelvic floor.

FIG. 8 shows three panel images illustrating the positions of sensorsS1-S10 (see, e.g., FIG. 3D) of an intravaginal device in a subjectduring pelvic floor relaxation (left panel), during Valsalva maneuver(middle panel), and during pelvic floor lift (right panel). The bottomdashed line indicates the position of the virtual plane of the introitusduring each maneuver. The three dashed lines in the upper portionillustrate the position of the posterior fornix sensor during eachmaneuver. During Valsalva maneuver, the posterior fornix sensor movesdown 1.6 cm relative to its position during pelvic floor relaxation.During a pelvic floor lift, the posterior fornix sensor moves up 0.5 cmrelative to its position during relaxation. The data were generatedusing MEMS sensors and the images were created by a processing devicebased on the sensor data.

FIG. 9 is a graph plotting, on the ordinate, the sensor angle forsensors S1-S8 (degrees) and, on the abscissa, time (seconds) duringwhich a subject performed a series of maneuvers as indicated by thevertical lines (pelvic floor relaxation, Valsalva maneuver, pelvic floorlift, sustained pelvic floor lift (hold), and serially repeated pelvicfloor lift (repeat)). Sensor 5 showed the largest change in sensor angleduring maneuvers. The sensor data were generated using MEMS sensors.

FIGS. 10A-10B are a set of graphs plotting, on the ordinate, sensorangle composite scores (Y1 and Y2) and, on the abscissa, time (seconds)during which a subject performed a series of maneuvers as indicated bythe vertical lines (pelvic floor relaxation, Valsalva maneuver, pelvicfloor lift, sustained pelvic floor lift (hold), and serially repeatedpelvic floor lift (repeat)). FIG. 10A shows the sensor angle plotted asa function of time, and FIG. 10B shows the first derivative with respectto time of the data in FIG. 10A, showing a change in the sensor angle asa function of time.

FIG. 11 is a graph showing the change in sensor angle for each sensor in10 different subjects. Each bar represents a change in sensor angle(angle during lift−angle during relaxation) for each of sensors S1-S10for each subject. The horizontal lines indicate the mean sensor anglefor a given sensor. S4-S6 provide the strongest, and most consistentsignal to noise ratio, magnitude, and directionality. The sensorproviding the strongest signal and the vaginal length is indicated foreach user. For three users, the “Trained” label reflects that the userexhibits indicia indicating the absence of a pelvic floor disorder.

DETAILED DESCRIPTION OF THE INVENTION

The invention features devices, systems, and methods for training thepelvic floor muscles of an individual (e.g., a female patient), therebytreating or reducing the likelihood of developing a PFD, or for treatinga vaginal disorder, in particular, using an intravaginal device. Theintravaginal device described herein can be used to measure anindividual's performance of a PFL and/or PFR using one or more sensorswithin the device. The invention also features peripheral devicescomprising a computer processing unit configured to collect data fromthe sensors on the intravaginal device and transform the data intouseful physiological indicia representative of a health state or theoccurrence of a predetermined event. The data may then be presented tothe user or another subject to provide feedback or alerts regarding thephysiological indicia. The peripheral device may be configured with oneor more algorithms that analyzes positional data from the sensors. Theintravaginal device may be configured to provide monitoring of theoverall health status of a user's urogenital system and pelvic floor(e.g., the muscle fibers of the levator ani, e.g., the pubococcygeus,ileococcygeus, coccygeus, puborectalis muscles and associated connectivetissues) in substantially real-time, e.g., while a user performs herdaily activities. The device can also provide biofeedback to theindividual following or during use. The device and system can beconfigured to coach the individual to perform a PFL and/or PFR correctlyand to guide them to reach therapeutic goals, such as reduced PFDsymptom occurrence and/or severity. Exemplary intravaginal devices,systems, and methods for training, visualizing, and diagnosing thehealth state of pelvic floor muscles of an individual have beenextensively described in International Publication Nos. WO2013116310,WO2015103629, and WO2018023037, the disclosures of which are herebyincorporated in their entirety.

Various methods have been proposed to improve the strength and tone ofthe pelvic floor muscles, such as pelvic floor muscle training (PFMT),yet many of these methods do not target and activate the correct pelvicfloor muscles. The devices, systems, and methods described herein can beused to train an individual to perform PFMT exercises characterized byeither a lifting (e.g., upward) movement of the pelvic floor or alowering (e.g., downward) movement of the PF, which are referred toherein as a pelvic floor lift (PFL) and a pelvic floor relaxation (PFR),respectively. Training a patient to perform a PFL and/or a PFR can leadto improvements in both the strength and the quality of the pelvic floormuscles, resulting in a therapeutic benefit for individuals having aPFD.

The intravaginal device may also be used alone or in combination with aperipheral device that is configured to receive sensor data from theintravaginal device to monitor (e.g., with one or more sensors asdescribed herein) the overall health status of a user, including theuser's urogenital system and pelvic floor (e.g., the muscle fibers ofthe levator ani (e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues) in substantiallyreal-time, e.g., while a user performs her daily activities. Forexample, an intravaginal device of the invention may be configured todetect when a user performs a daily activity that alters (e.g.,increases and/or decreases) the overall health of her urogenital systemand/or pelvic floor and may provide feedback to the user, e.g., on howthe detected activity affects her health status. Alternatively, theperipheral device may be configured with a processing unit that cantransform or utilize sensor data received from the intravaginal devicewhen a user performs a daily activity (e.g., activity that alters (e.g.,increases and/or decreases) the overall health of her urogenital systemand/or pelvic floor) to provide feedback to the user (or a health careprovider) regarding whether the detected activity affects her healthstatus. For example, the peripheral device can process the sensor datato produce a baseline that can be used for comparison to sensor dataobtained at a future time to provide feedback to the user (e.g., analert) regarding whether an event (e.g., activities she performs duringher daily routine, such as a pelvic floor movement) is beneficial ordetrimental to her health status. In addition, or alternatively, theperipheral device can process the sensor data and compare the result toa previously established or predetermined baseline and based on thecomparison can provide feedback to the user (e.g., an alert) regardingwhether an event (e.g., activities she performs during her dailyroutine, such as a pelvic floor movement) is beneficial or detrimentalto her health status. A user may review the feedback in substantiallyreal-time (e.g., the user may receive an alert noting her health statusor a change in her health status) or she may review feedback at a latertime of her choosing, e.g., by accessing feedback stored in the memoryof the intravaginal device, in the memory of a peripheral device (e.g.,a computer, phone (e.g., as an alert, an email, or a text message), ortablet that is or can be connected to the intravaginal device), and/orin the memory of a remote electronic device (e.g., a web-located and/orcloud-based database connected to the intravaginal device). Feedback maybe presented as a summary, e.g., as one or more graphs, showing how auser's daily activities and detected vaginal conditions (e.g., pH,temperature, pressure, moisture level, muscle movement (e.g., a PFLand/or a PFR), muscle quality, muscle strength, and/or the level of amolecule, such as a hormone and/or toxin) affected the overall healthstatus of a user's urogenital system and/o pelvic floor over time (e.g.,over a period of time, such as a period of about 1 to about 60 minutes,about 1 to about 24-hours, about 1 to about 31 days, about 1 to about 24months, or about 1 or more years). Daily monitoring, as describedherein, may help a user to optimize treatment with an intravaginaldevice of the invention, to avoid the development and/or reoccurrence ofa PFD, or the symptoms thereof, and/or to inform a user on thedevelopment and/or progression and/or treatment status of an additionalcondition or disorder of the female pelvic floor or urogenital tract.

The intravaginal device of the invention may be configured with one ormore energy transmitters and used to administer energy to vaginaltissue, which may be used in therapeutic applications to treat a pelvicfloor or vaginal disorder. Exemplary vaginal disorders are vaginallaxity, pelvic organ prolapse, incontinence, tissue tone (e.g., moistureand tightness), nerve sensitivity, orgasmic dysfunction, vulvovaginallaxity (e.g., in labial and vaginal tissues), atrophic vaginitis, stressincontinence, and pubocervical fascia tightening. The energytransmitters may be, for example, radio frequency transmitters, lasers,or electrical stimulators. RF transmitters provide nonablative radiofrequency in the form of thermal energy to treat vaginal and pelvicfloor disorders by heating tissue. By applying heat to the affectedtissue, the thermal damage stimulates collagen production in deep layersof the skin and subcutaneous tissue to strengthen and fortify thecollagen network in the vagina and surrounding area. This strengthensthe tissues in areas critical for maintaining pelvic floor and vaginalhealth. The intravaginal device of the invention may be configured withor without this therapeutic capability.

Additionally, an intravaginal device of the invention may be configuredto administer or deliver at least one (e.g., 1, 2, 3, 4, 5, or more)pharmaceutical agent, e.g., a pharmaceutical agent useful in thetreatment of a PFD or a symptom thereof (e.g., to promote a change inmuscle tone and/or muscle strength, or to reduce bladder leakage(including frequency and urgency of urination), anal or fecal leakage,or pain. The device may also be configured to treat an additionalcondition, disease, and/or related symptom present in an individualhaving a PFD, e.g., a condition, disease, or related symptom affecting avaginal tissue and/or an organ or tissue of a female subject.Non-limiting examples of an additional condition, disease, or symptomthat may be treated by an intravaginal device of the inventionconfigured to deliver a pharmaceutical agent include a sexuallytransmitted disease (STD), a yeast infection (e.g., candidavulvovaginitis), a bacterial infection (e.g., bacterial vaginosis), aparasitic infection (e.g., trichomoniasis), an infection of the cervix(e.g., cervicitis), a cancer (e.g., vaginal, vulva, cervical, ovarian,endometrial, and/or fallopian tube cancer), vaginitis (e.g., infectiousand/or noninfectious vaginitis), endometriosis, vaginal pain, vulvarpain (e.g., vulvodynia), a vulvar or vaginal injury, pudendal neuralgia,and/or a vaginal skin condition (e.g., vaginal dermatitis). Anintravaginal device configured to deliver a pharmaceutical agent, may beformed from biocompatible polymers and contain a pharmaceutical agentreleased, e.g., by diffusion through the polymer matrix. In someinstances, the pharmaceutical agent may be uniformly dispersed ordissolved throughout the polymer matrix (e.g., of the main body and/ortether of an intravaginal device of the invention) in a designconfiguration that is referred to in the art as a “monolithic system.”In some instances, the drug may be confined to an inner core within themain body and/or tether of an intravaginal device of the invention in adesign configuration that is referred to in the art as a “reservoirsystem.”

An intravaginal device of the invention configured to deliver apharmaceutical agent may be inserted into the vaginal cavity and thepharmaceutical agent may be absorbed by the surrounding body fluidthrough the vaginal tissue, e.g., over a treatment period. Intravaginaldevices of the invention configured as monolithic systems may exhibit,e.g., Fickian diffusion-controlled pharmaceutical agent release, wherebythe release rate decreases with time. Intravaginal devices of theinvention configured to contain a reservoir system may exhibit a zeroorder release of a pharmaceutical agent.

Use of an intravaginal device of the invention that is configured todeliver a pharmaceutical agent may result in an enhanced therapeuticbenefit for an individual having a PFD when combined with pelvic floortraining (e.g., the performance of a PFL and/or PFR), e.g., as comparedto the therapeutic benefit achieved through use of an intravaginaldevice to perform pelvic floor exercises that is not configured todeliver a pharmaceutical agent). Monitoring the overall health status ofa user's urogenital system and/or pelvic floor (e.g., the muscle fibersof the levator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues), with the optionof receiving instantaneous (e.g., substantially real-time) feedback, mayhelp a user to optimize and/or enhance the efficiency of a treatmentregime including a pharmaceutical agent (e.g., a pharmaceutical agentdelivered by an intravaginal device of the invention or administered,e.g., by the user, in combination with the use of an intravaginal deviceof the invention). For example, an intravaginal device of the inventionmay be configured to identify a poor health status based on datacollected from one or more sensors (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,or more sensors) of the intravaginal device that are configured tomeasure a metric, e.g., a muscle movement (e.g., a PFL and/or PFR),muscle strength, muscle quality, pressure, pH, temperature, biomoleculelevel (e.g., a hormones and/or a toxin), and/or moisture level(humidity) and to deliver a pharmaceutical agent automatically or tosignal to the user the need or benefit of delivering the pharmaceuticalagent.

I. Pelvic Floor Lifts (PFLs) and Pelvic Floor Relaxations (PFRs)

The pelvic floor (PF), also referred to as the pelvic floor diaphragm,is predominantly formed by the muscle fibers of the levator ani (e.g.,the pubococcygeus, ileococcygeus, coccygeus, and puborectalis muscles)and the associated connective tissues which span the area underneath thepelvis (Bharucha. Neurogastroenterol Motil. 18:507-519, 2006). Thepelvic floor lift (PFL) is an exercise characterized by an upwardmovement (e.g., a lifting movement, e.g., a movement in the cranialdirection) of the pelvic floor. A closely related movement comprising arelaxation (e.g., a downward movement, e.g., a movement in the caudaldirection) of the pelvic floor is a pelvic floor relaxation (PFR). Themovement of the pelvic floor during the performance of a PFL and/or aPFR may be distinct from the movement of the pelvic floor during theperformance of a Kegel exercise. The Kegel movement, developed by Dr.Arnold Kegel, may be described as a contraction of the vaginal channeldiameter (e.g., a squeezing movement of the vaginal walls, e.g., amovement of the vaginal walls in the dorsal-ventral oranterior-posterior) direction). During a PFL and a PFR the pelvic floormay be described as raising and lowering, respectively, the vaginalcanal. This raising or lowering of the vaginal canal during a PFL andPFR may be due to the lifting and relaxing of the pelvic floor muscles.

Training an individual to perform PFLs and/or PFRs can improve thestrength and muscle quality of the pelvic floor resulting in therapeuticbenefit to individuals having pelvic floor disorders (PFDs). Examples ofpelvic floor disorders that can be treated, prevented, and/orameliorated by training an individual to perform PFLs and/or PFRs arefurther described herein.

Proper performance (e.g., accurate execution) of a PFL and/or PFR can beused to prevent injury to the pelvic floor during pelvic floor muscletraining (PFMT). An individual contracting the pelvic floor muscles,such as by improperly performing a Kegel movement, may strain, damage,or otherwise reduce the effectiveness of PFMT with PFLs and/or PFRs. Inparticular, patients that bear down can create strain that can promotefurther damage to the pelvic floor. Therefore, to achieve maximumtherapeutic benefit and to increase the efficacy of PFMT with PFLsand/or PFRs an intravaginal device of the invention, configured to senseand provide feedback on the accurate performance of a PFL and/or PFR,can be used along with PFLs and/or PFRs training as a therapeutic orprophylactic treatment for a PFD (e.g., to reduce the occurrence and/orseverity of at least one symptom of a PFD).

A PFL and/or PFR can be identified and measured by an intravaginaldevice of the invention, which places a sensor within the vaginal cavityof an individual, specifically at a location proximal to the cervix orvaginal cuff. The sensor positioned at a location proximal to the cervixor a vaginal cuff is configured to detect movement of the pelvic floorin the cranial-caudal direction (e.g., lifting and/or relaxationmovements of the PF) to detect (e.g., to measure) the performance andquality of a PFL and/or PFR executed by an individual. In devicesutilizing a tether, the main body may or may not have a sensor and isconfigured to position a sensor(s) in the tether within the vaginalcanal for measurement of a PFL and/or PFR. The devices, which aredescribed further herein, can be used to treat, prevent, and/orameliorate at least one symptom of a PFD.

Monitoring the overall health status of a user's urogenital systemand/or pelvic floor (e.g., the muscle fibers of the levator ani, e.g.,the pubococcygeus, ileococcygeus, coccygeus, puborectalis muscles andassociated connective tissues) in substantially real-time may allow forthe identification of daily activities that may affect, e.g.,negatively, the health status of the user. For example, an intravaginaldevice of the invention may be configured to identify a poor healthstatus based on data collected from one or more sensors (e.g., 1, 2, 3,4, 5, 6, 7, 8, 9, 10, or more sensors) of the intravaginal device thatare configured to measure a metric, e.g., muscle movement (e.g., a PFLand/or PFR), muscle strength, muscle quality, pressure, pH, temperature,biomolecule level (e.g., a hormones and/or a toxin level), and/orhumidity, and to signal to the user the need or benefit of ceasingperformance of the detected activity. In some instances, a detectedmetric, e.g., a muscle movement, may be beneficial to the health statusof a user and may increase the efficiency of the user's establishedtraining program. In this case, the device can be configured to conveyto the user the benefit of continuing or repeating the activity orbehavior that provided the detected metric.

The intravaginal device may be configured to communicate with aperipheral device configured to analyze the data collected from thesensors on the intravaginal device and transform the data into usefulphysiological indicia representative of a health state or the occurrenceof a predetermined event (e.g., a pelvic floor movement or other eventdescribed herein). The peripheral device may have a processor thatexecutes instructions of a stored program(s) (e.g., one or morealgorithms) that analyzes positional data from the sensors. Theperipheral device can be configured to alert the user (or a health careprovider) or as to their health status during or following routine dailyactivities (e.g., during or following an event, such as during and/orafter performing a pelvic floor movement), and/or the peripheral devicecan be configured to present the data or an indication of the healthstatus of the user (e.g., on a graphical user interface or display)during routine daily activities and/or while performing, or after theperformance of, a pelvic floor movement.

In some instances, a detected metric, e.g., a muscle movement, maynegatively affect the health status of a user (e.g., the muscle movementmay reduce the efficiency of the user's established training program fortreating or reducing the likelihood of developing a PFD). In this case,the device (e.g., the peripheral device) can be configured to convey tothe user (e.g., based on the peripheral device performing an algorithmto analyze data from the sensors of the intravaginal device) thenegative effect of continuing or repeating the activity or behavior thatprovided the detected metric.

In some instances, a detected metric, e.g., a muscle movement, a levelof or change in the level of muscle strength, muscle quality, a hormone,a toxin, pH, temperature, and/or humidity may be used to diagnose and/orpredict the development of a PFD and/or an additional disease orcondition, as described herein, according to known methods known in theart. The peripheral device may also be configured to signal to the user(e.g., based on the peripheral device performing an algorithm to analyzethe data from the sensors of the intravaginal device) and/or the medicalpractitioner overseeing the user's treatment the need or benefit ofaltering the training program to reduce the impact of a user's dailyactivities or behaviors that negatively affect her health status and/orto address a new PFD and/or disease or condition that has developed inthe user.

II. System and Device for Training a User to Perform a Pelvic Floor Lift(PFL) and/or Pelvic Floor Relaxation (PFR)

The intravaginal device described herein, which has a main body and/or atether, can be used as part of a training system for performing a pelvicfloor lift (PFL) and/or pelvic floor relaxation (PFR). The device isinserted into an individual, such that the intravaginal device ispositioned proximal to the cervix or vaginal cuff, and is configured totreat, inhibit, and/or reduce the development of or progression of apelvic floor disorder (e.g., urinary incontinence (UI), stress urinaryincontinence (SUI), urge incontinence, mixed stress and urge urinaryincontinence, dysuria (e.g., painful urination), anal or fecalincontinence, pelvic organ prolapse (POP) (e.g., urethra (urethrocele),bladder (cystocele), or both (cystourethrocele), vaginal vault andcervix (vaginal vault prolapse), uterus (uterine prolapse), rectum(rectocele), sigmoid colon (sigmoidocele), and small bowel(enterocele)), pelvic pain, sexual dysfunction (e.g., coitalincontinence, a sexual pain disorder, dyspareunia, vaginismus, and/orimpaired sexual arousal), weak or impaired pelvic floor muscle function,post-labor issues or damage, pain and/or incontinence caused by damageto a lumbosacral nerve, and nonrelaxing pelvic floor dysfunction) in anindividual when used according to the methods described herein.

The intravaginal device has a main body with an outer edge configured tocontact all or a portion of the vaginal wall surrounding the cervix orvaginal cuff and has an internal diameter sized to approximatelycircumferentially surround a cervix or a vaginal cuff. The internal andexternal diameter of the intravaginal device may be approximatelyequivalent, with the difference in their length being attributable tothe thickness of the material used to fabricate the intravaginal device.The internal and/or external diameter may be about 20 mm to about 80 mm(e.g., about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mm)in length. In some instances, the internal diameter of the intravaginaldevice may be smaller than the external diameter. In some instances, theintravaginal device can be fabricated with a tether (e.g., a flexiblecord or ribbon) that can be optionally attached, e.g., by a removable orpermanent connection, to the main body of the intravaginal device, Thetether can have a length of up to about 14 cm (e.g., 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, or 14 cm) and a width of about 1 to about 10 mm(e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mm). Different form factors ofthe device include a ring (round or oval), a ring with a tether, and anincomplete ring (e.g., a horseshoe configuration). The intravaginaldevice may have the structure as described in International PublicationNos. WO2013116310, WO2015103629, and WO2018023037, the disclosures ofwhich are hereby incorporated by reference.

The intravaginal device (e.g., main body and/or tether) can be made froma flexible, biocompatible material, such as a material selected from thegroup consisting of, but not limited to, silicone, polyethylene,polypropylene, polystyrene, polyester, polycarbonate, polyvinylchloride, polyethersulfone, polyacrylate, hydrogel, polysulfone,polyetheretherketone, thermoplastic elastomers, poly-p-xylylene,fluoropolymers, rubber, and latex. The intravaginal device may befabricated to be solid, hollow, and/or partially filled. Additionally,the intravaginal device may contain metal and/or plastic components,such as a core, ring, spring, and/or wire. The metal and/or plasticcomponents may be used to provide additional tension (e.g., a pushingforce) on the vaginal walls to maintain the position of the intravaginaldevice when inserted into an individual when incorporated into the mainbody of the intravaginal device. In some instances, the intravaginaldevice is fabricated out of silicone. However, other suitable materialsmay be used to fabricate the intravaginal device.

The main body of the intravaginal device may be cup-shaped and includean optional permeable or semi-permeable membrane, mesh, and/orperforated barrier in the central portion of the device (e.g., spanningthe internal diameter). In other instances, the intravaginal device maybe a sponge and may include a depression for cupping the cervix orvaginal cuff. In some instances, in which the intravaginal device has adonut shape, the intravaginal device may include an optional permeableor semi-permeable membrane, mesh, and/or perforated barrier. The barriermay extend across the internal diameter of the donut-shaped intravaginaldevice.

The outer edge of the main body of the intravaginal device may beconfigured to apply pressure, tension, adhesion, and/or suction to thevaginal wall to hold the position of the intravaginal device at alocation proximal to the cervix or vaginal cuff of the individual. Thepressure, tension, adhesion, and/or suction applied to the vaginal wallby the outer edge of the intravaginal device is of a sufficient strengthto limit slippage, repositioning, or displacement of the intravaginaldevice from the vaginal canal of individual.

Additionally, the main body of the intravaginal device may include atleast one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) feature for thepurpose of stabilizing, orienting, and/or positioning the device withinthe body of the individual. The feature may be selected from the groupconsisting of a coating, a protrusion, and a texture. In some instances,the feature is a coating (e.g., a surface coating) containing one ormore one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) biomaterials. Ina particular instance, the coating may be provided, such as within akit, in a sealed packet for the individual to apply to the intravaginaldevice prior to insertion. In some instances, the feature is aprotrusion or a series of protrusions having the shape of a wing,sphere, bump, knob, raised lined, and/or raised dot. In some instances,the feature is a texture, such as a sticky, rough, grooved, or pittedsurface texture. The main body may also include indicia (e.g., aprotrusion, symbol, writing, or etching) identifying the cranial (e.g.,top), caudal (e.g., bottom), anterior (e.g., front), posterior (e.g.,back), right, and left sides of the intravaginal device. Theintravaginal device should be positioned within the body of theindividual such that the top side sits proximal to the top of thevaginal canal (e.g., proximal to the cervix or vagina cuff), and theanterior side faces the front of the body. Examples of features to aidin retention are a bulbous extrusion at the top or bottom of the deviceand a form having protruding arms. The retention features may be appliedas in the devices shown or they can be applied as features to otherdevices described herein, The retention features may be useful for adevice of the invention that is designed to remain inside a woman'svagina for an extended period of time (e.g., at least 10 minutes, 20minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 2 hours, 3 hours, 4hours, 5 hours, 6 hours, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10months, 11 months, 12 months).

The intravaginal device includes at least one (e.g., 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 20, or more) sensor within the main body (e.g., thesubstantially ring shaped form) and/or the tether that is configured todetect a muscle movement, e.g., a PFL and/or a PFR. In some instances,the sensor may be configured to detect a muscle movement, e.g., a PFLand/or a PFR, which is performed during a user's daily activities, insubstantially real-time. Daily activities may be identified by theintravaginal device as either contributing positively or negatively tothe overall health of a user's urogenital system and/or pelvic floor(e.g., the muscle fibers of the levator ani, e.g., the pubococcygeus,ileococcygeus, coccygeus, puborectalis muscles and associated connectivetissues). In some instances, the at least one sensor (e.g., 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 20, or more sensors) may be selected from the groupconsisting of a movement sensor, an orientation sensor, anaccelerometer, a gyroscope, a micro-electro-mechanical systems (MEMS)sensor, a G-sensor, a tilt sensor, a rotation sensor, a pressure sensor,a light detecting sensor, such as a LiDAR sensor, an EIM sensor, andcombinations thereof. The device may also include a light generatingcomponent for use with the light detecting sensor, such as a LiDARsensor. The device may also include an electrode for use with the EIMsensor. Additionally, the intravaginal device may include one or moresensors (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or more sensors)configured to detect, e.g., a level of or change in the level of musclestrength, muscle quality, a biomolecule (e.g., a hormone and/or atoxin), pH, temperature, and/or humidity.

In some instances, the sensors may be positioned in an arrangementsimilar to or in an arrangement different from those described inInternational Publication Nos. WO2015103629A1, WO2016067023A1, andWO2016042310A1; U.S. Publication Nos. US20150032030A1, US20140066813A1,US20150151122A1, US20150133832A1, US20160008664A1, and US20150196802A1;and U.S. Pat. Nos. 8,983,627, 7,955,241, 7,645,220, 7,628,744,7,957,794, 6,264,582, and 6,816,744, each of which is incorporated byreference herein. For example, two or more sensors, as described herein,may be placed around the longitudinal axis of the intravaginal device,e.g., in a circle or a spiral around the central-axis of the main bodyand/or tether of the intravaginal device, approximately at ±1°, 2°, 3°,4°, 5°, 6°, 7°, 8°, 9°, 10°, 20°, 30°, 40°, 50°, 60°, 70°, 80°, 90°,100°, 110°, 120°, 130°, 140°, 150°, 160°, 170°, 180°, 190°, 200°, 210°,220°, 230°, 240°, 250°, 260°, or 270° relative to each other.Alternatively, or additionally, two or more sensors, as describedherein, may be placed approximately 0.001 mm, 0.01 mm, 0.1 mm, 0.5 mm, 1mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 20 mm, 30 mm,40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 125 mm, 150 mm, 175mm, 200 mm, 225 mm, 250 mm, 275 mm, 300 mm, 325 mm, 350 mm, or moreapart, e.g., along the circumference of the main body and/or along thelength of the tether of the intravaginal device. In some instances, thetwo or more sensors, as described herein, may be placed along thecentral-axis of the main body and/or tether of the intravaginal device.In some instances, the two or more sensors, as described herein, may beplaced such that they are not on the central-axis, e.g., such that theyare offset from the central axis of the main body and/or tether of theintravaginal device. In particular instances, such as when sensors arepositioned within the tether, the main body may not contain a sensor. Inother instances, when sensors are positioned within the tether the mainbody may also contain at least one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,20, or more) sensor. The at least one sensor (e.g., 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 20, or more sensors) may be selected from the group consistingof a movement sensor, accelerometer, gyroscope, micro-electro-mechanicalsystems (MEMS) sensor, G-sensor, tilt sensor, rotation sensor, a lightdetecting sensor, such as a LiDAR sensor, an EIM sensor, andcombinations thereof. The device may also include an electrode and/or alight generating component. In some instances, the sensor is anaccelerometer, such as a multiple-axis accelerometer. In otherinstances, the sensor is a gyroscope, such as a multiple-axis gyroscope.In yet other instances, the sensor is a MEMS sensor. Additionally, theintravaginal device may further include at least one (e.g., 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 20, or more) additional sensor within the main bodyand/or the tether selected from the group consisting of a pressuresensor, a muscle quality sensor, a muscle strength sensor, a biomoleculesensor (e.g., a hormone sensor and/or a toxin sensor), a temperaturesensor, a humidity sensor, and a pH sensor. A sensor(s) can bepositioned on the surface of the intravaginal device (e.g., on thesurface of the main body and/or tether), such that all or a portion ofthe sensor(s), makes direct contact with the tissues of the vaginalwalls and/or cervix or vaginal cuff of an individual. In some instances,the sensor(s) can be positioned about 0.001 mm, 0.01 mm, 0.1 mm, 0.2 mm,0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.5 mm, 2mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm, or more below the exteriorsurface (e.g., the surface that makes direct contact with the tissues ofthe vaginal walls and/or cervix or vaginal cuff of an individual) of theintravaginal device (e.g., the main body and/or tether of theintravaginal device). In some instances, the sensor can be positionedsuch that about 0.001 mm, 0.01 mm, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm,3.5 mm, 4 mm, 4.5 mm, 5 mm, or more of the sensor protrudes from theexterior surface of the intravaginal device (e.g., the main body and/ortether of the intravaginal device). Alternatively, the sensors can bepositioned within the intravaginal device (e.g., within the main bodyand/or tether), such that the sensor does not directly contact thevaginal walls and/or cervix or vaginal cuff of an individual, but arepositioned to detect motion as the user conducts a PFL or PFR.

As the intravaginal device (e.g., the main body and/or tether) can befabricated to be solid, hollow, or partially filled, a sensor that doesnot make direct contact with the vaginal walls/and or cervix or vaginalcuff of an individual may be positioned at a depth within the solidmaterial from which the intravaginal device (e.g., the main body and/ortether) was fabricated or within a hollow space of the intravaginaldevice (e.g., main body and/or tether). The sensor(s) may be evenly orunevenly positioned at intervals on or within the intravaginal device.The sensors within the intravaginal device (e.g., within the main bodyand/or tether) may be positioned such that when the intravaginal deviceis inserted into a user the sensors face the ventral direction (e.g.,anterior direction).

The tether can be up to about 14 cm (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, or 14 cm) in length and may be divided along its lengthinto segments contain sensors. Sensors can be positioned along thelength of the tether at even or uneven intervals, e.g., at an intervalof about 1 to about 140 mm (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30,40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 mm). The location ofa sensor within the tether may be identified on the outside of thedevice by the presence of indicia (e.g., a protrusion, symbol, writing,and/or etching) on the surface of the tether. The tether may be designedto be trimmed, e.g., by cutting with scissors, so that an individual canreduce the tether to a comfortable length. The indicia indicating thelocation of a sensor can help guide the individual to avoid cutting asensor.

The intravaginal device (e.g., main body (e.g., the substantially ringshaped form) and/or tether) further includes a microcontroller withinthe substantially ring shaped form that is configured for receiving datafrom the sensor(s). The microcontroller may also be configured, or caninclude a separate component, for non-transiently storing data from thesensor(s). The microcontroller maybe connected to the sensor(s), e.g.,by a wire and/or a circuit board. The wire and circuit board may beflexible or rigid.

The intravaginal device can also include a transmitter and receiverwithin main body (e.g., the substantially ring shaped form) and/ortether form for communicating wirelessly or via a detachable cable withan electronic device (e.g., a peripheral device, such as a handheld orportable device or a computer, such as a smartphone, tablet, or laptop).Alternatively, the transmitter and receiver may be located in anexternal housing and connected to the intravaginal device wirelessly orby a detachable cable. The transmitter and receiver can be connecteddirectly or indirectly to the microcontroller, sensor(s), and/or circuitboard. The transmitter and receiver can be configured for use with aBluetooth-, and/or Wi-Fi-, and/or RF-enabled electronic device.Information collected by the sensor(s) may be communicated (e.g.,downloaded, transferred) to the electronic device wirelessly by thetransmitter and receiver and/or by using the detachable cable.

The electronic device may be a computer, tablet, and/or smartphone(e.g., an iPhone, an iPad, an iPod Touch, an Android-based system, aMicrosoft Windows-based system, or other equivalent device). Theelectronic device can be connected wirelessly (e.g., through aBluetooth, and/or Wi-Fi, and/or RF connection) to the intravaginaldevice and/or by a detachable cable. The electronic device can beconfigured to receive and/or process data measured by the sensor(s) ofthe intravaginal device. Alternatively, the electronic device can beconfigured to communicate (e.g., through a wired or wireless connection,e.g., through a Bluetooth, Wi-Fi, and/or internet connection) with adatabase that contains data collected by the intravaginal device or withanother system that receives and processes the data and conveys theinformation to the electronic device. Data collected by the intravaginaldevice, such as data collected by the sensor(s), may be storednon-transiently on the electronic device. The data may be transmitted(e.g., transmitted after a training period, substantially in real-time,and/or at least once daily upon activation by the user) to a database(e.g., a database stored on a different computer, such as a web-locatedand/or cloud-based database). The data may include a performance metricand/or scoring information, such as a score assigned to a musclemovement, e.g., a PFL and/or PFR, performed by the individual that isreflective of the quality of the muscle movement, e.g., a PFL and/orPFR, performed as compared to a calibrated baseline from the individual.The data may include one or more, or all, of the highest and lowestscores achieved by an individual over a training period, an averagescore achieved by an individual over a training period, the length oftime over which a particular score was maintained by an individual, theraw data collected from the sensor(s), the start time of and the lengthof the training period, maximum PFL and/or PFR duration, the current pH,the average, lowest, and highest pH reached by an individual over thetraining period, a score related to muscle quality.

Additionally, the system can include a peripheral device, which may beconfigured with a processing unit that can transform or utilize sensordata received from the intravaginal device when a user performs a dailyactivity (e.g., activity that alters (e.g., increases and/or decreases)the overall health of her urogenital system and/or pelvic floor) toprovide feedback to the user regarding whether the detected activityaffects her health status. For example, the peripheral device canprocess the sensor data to produce a baseline that can be used forcomparison to sensor data obtained at a future time to provide feedbackto the user (e.g., an alert) regarding whether activities she performsare beneficial or detrimental to her health status. In addition, oralternatively, the peripheral device can process the sensor data andcompare the result to a previously established or predetermined baselineand based on the comparison can provide feedback to the user (e.g., analert) regarding whether activities she performs are beneficial ordetrimental to her health status.

Additionally, the data may include a performance metric and/or scoringinformation, such as a score assigned to the overall health status of auser's urogenital system and/or pelvic floor (e.g., the muscle fibers ofthe levator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues). The healthstatus score may be derived from data collected, e.g., from anintravaginal device of the invention configured to monitor a user'surogenital system and/or pelvic floor in substantially real-time, whichis an optional monitoring state (“Live Mode”), as a user performs herdaily activities, e.g., by one or more sensors selected from the groupconsisting of a movement sensor, an orientation sensor, anaccelerometer, a gyroscope, a micro-electro-mechanical systems (MEMS)sensor, a G-sensor, a tilt sensor, a rotation sensor, a pressure sensor,a light detecting sensor, such as a LiDAR sensor, an EIM sensor, ahormone sensor, a toxin sensor, a pH sensor, a temperature sensor,and/or a humidity sensor, and combinations thereof. A health statusscore may indicate to a user whether a particular daily activity and/ormetric contribute positively or negatively to the overall health of theuser's urogenital system and/or pelvic floor.

The database may be located on the electronic device, on an additionalelectronic device, or on the Internet (e.g., a web-located and/orcloud-based database). The electronic device may be connected to thedatabase by a detachable cable, a Bluetooth connection, a Wi-Ficonnection, and/or an internet connection. Communication with aparticular type of electronic device, such as an Apple device, mayrequire the use of a special authentication chip.

Additionally, the electronic device can include a user interface. Theuser interface can be programmed to display data and/or to provideinstructions for use of the intravaginal device.

The intravaginal device (e.g., main body (e.g., the substantially ringshaped form) and/or tether) further includes a power source (e.g., abattery). The power source can be used to operate one or more componentsof the device, such as the sensor(s), transmitter, receiver, and thecircuit board. In some instances, the power source is positioned withinthe substantially ring shaped form of the intravaginal device andconnected to the component(s) by a wire and/or by a circuit board. Thepower source may be a rechargeable battery, such as a nickel-cadmiumbattery or a lithium ion battery, such as one compatible with wired orwireless (e.g., inductive) charging. Additionally, the external housingmay include a power source connected to the transmitter or receiver,e.g., by a wire and/or by a circuit board. An ON/OFF switch can also beincluded.

The intravaginal device may further include a detachable cable connectedto sensor(s) either directly or indirectly, e.g., by a wire or a circuitboard. The detachable cable may also be configured to connect theintravaginal device to an electronic device. The detachable cable mayalso be configured to assist in the removal of the intravaginal devicefrom its position within the vaginal canal (e.g., proximal to the cervixor vaginal cuff) of a user. In some instances, the detachable cable isthe tether.

The intravaginal device may further include within the main body (e.g.,the substantially ring shaped form) and/or tether a sensory outputcomponent for providing biofeedback to an individual. The sensory outputcomponent may be connected to the microcontroller and/or the sensor(s),e.g., by a wire and/or by a circuit board. The biofeedback relates to atleast one performance metric as measured by the sensor(s). Theperformance metric can be proper execution of a PFL and/or a PFR,duration of time in which the intravaginal device has been in use (e.g.,the time in which the intravaginal device has been at a positionproximal to the cervix or vaginal cuff of the user (i.e., totalinsertion time), the time over which PFLs and/or PFRs have beenperformed, (i.e., total training time)), pH, and/or muscle quality. Aperformance metric may be a measurement of the overall health status ofa user's urogenital system and/or pelvic floor (e.g., a measurement ofmuscle movement, muscle quality, muscle, strength, a biomolecule level(e.g., a hormone and/or a toxin level), pH, temperature, and/orhumidity) obtained during daily monitoring (e.g., in substantiallyreal-time) with an intravaginal device as the user performs her dailyactivities. The sensory output component may be configured to produce avisual, vibrational, and/or auditory signal as the biofeedback. Theintravaginal device may be configured to notify the user when to removethe intravaginal device.

The intravaginal device may be configured for use with a tool forinsertion. The tool for insertion is capable of deforming theintravaginal device and/or deploying the intravaginal device at alocation within the user (e.g., at a position proximal to the cervix orvaginal cuff).

The device may be used at home, work, physician's office, clinic,nursing home, pelvic health or other center or other locations suitablefor the individual. A physician, nurse, technician, physical therapist,or central customer support may supply support for the patient/user.

Each of the components of the intravaginal device is described below.

Sensors that can be Used to Measure a Performance Metric and/or aCharacteristic of a Pelvic Floor Disorder (PFD)

Sensors that can be used in the intravaginal device (e.g., within themain body (e.g., the substantially ring shaped form) and/or tether) ofthe invention (e.g., to measure the occurrence and/or quality of pelvicfloor lifts (PFLs) and/or pelvic floor relaxations (PFRs) performed byan individual when the sensor is positioned at a location proximal tothe subject's cervix or vaginal cuff) include, but are not limited to,movement sensors, accelerometers, gyroscopes, micro-electro-mechanicalsystems (MEMS) sensors, G-sensors, tilt sensors, rotation sensors, lightdetecting sensors, such as light detecting and ranging (LiDAR) sensors,and electrical impedance myography (EIM) sensors. One (e.g., 1, 2, 3, 4,5, 6, 7, 8, 9, 10, or 20) or more sensors (e.g., movement sensors,accelerometers, gyroscopes, micro-electro-mechanical systems (MEMS)sensors, G-sensors, tilt sensors, rotation sensors, light-detectingsensors (e.g., LiDAR sensors), and EIM sensors) can be incorporated intothe main body of the intravaginal device and/or within a tether (e.g., aflexible cord or ribbon) that can be optionally attached, e.g., by aremovable or permanent connection, to the main body of the intravaginaldevice. The sensors may be arranged within the main body, tether, and/orsleeve of an intravaginal device of the invention. The sensors may bedistributed evenly or unevenly throughout the main body and/or tether,such that the distribution of the sensors allows for the measurement ofthe quantity and quality of PFL and/or PFR performed by an individualusing the intravaginal device. The device may also contain an electrodeand/or a light generating component.

The sensor(s) is configured to measure a movement of at least one muscleof the pelvic floor (e.g., the levator ani, e.g., the pubococcygeus,ileococcygeus, coccygeus, and/or puborectalis muscles) or associatedconnective tissue during a PFL and/or PFR. An intravaginal device of theinvention may be configured to provide daily monitoring, e.g., insubstantially real-time, of the overall health status of the urogenitalsystem and/or pelvic floor. An intravaginal device capable of providingdaily monitoring may contain one or more sensors selected from the groupconsisting of a movement sensor, accelerometer, gyroscope,micro-electro-mechanical systems (MEMS) sensor, G-sensor, tilt sensor,rotation sensor, a light detecting sensor, such as a light detecting andranging (LiDAR) sensor, and electrical impedance myography (EIM) sensor,a pressure sensor, a pH sensor, a humidity sensors, a temperaturesensor, a hormone sensor, and a toxin sensor. Such an intravaginaldevice may be able to identify changes in vaginal conditions that mayaffect a user's health, such as changes in the user's muscle qualityand/or muscle strength, a change in pH, in the level of a hormone and/ora toxin (e.g., a hormone and/or toxin level associated with a diseasestate, such as a PFD, a cancer, and/or a bacterial, fungal, or viralinfection). In some instances, the movement can be an upward movement(e.g., a lifting movement, e.g., a movement in the cranial direction) ofat least about 1-4 cm (e.g., about 1, 2, 3, or 4 cm). In some instances,the movement can be a downward movement (e.g., a dropping movement,e.g., a movement in the caudal direction) of at least about 1-4 cm(e.g., about 1, 2, 3, or 4 cm). The sensors within the intravaginaldevice (e.g., within the main body and/or tether) are positioned suchthat when the intravaginal device is inserted into a user the sensorsface the ventral direction (e.g., anterior direction). The sensor and/orcombination of sensors is capable of determining the orientation of theintravaginal device in the x, y, z-axis and can be configured to providefeedback to the individual when they have inserted the intravaginaldevice correctly.

In some instances, the device includes multiple sensors (e.g., 2, 3, 4,5, 6, 7, 8, 9, 10, or 20 sensors) of the same type (e.g., multiplemovement sensors, multiple accelerometers, multiple gyroscopes, multiplelight sensors, such as LiDAR sensors, or multiple electrical impedancemyography (EIM) sensors). In other instances, the device includesmultiple sensors of different types, such as a combination of differenttypes of sensors (e.g., at least two different types of sensors; e.g.,at least two different sensors selected from the following groups:movement sensors, accelerometers, gyroscopes, lights detecting sensors,such as LiDAR sensors, EIM sensors, micro-electro-mechanical systems(MEMS) sensors, G-sensors, tilt sensors, and rotation sensors). In aparticular instance, the device contains an accelerometer, such as amultiple-axis accelerometer, a gyroscope, such as a multiple-axisgyroscope, a MEMS sensor, and/or an EIM sensor. An exemplary sensor thatcan be used to measure PFLs and/or PFRs or muscles movements that occurwhile the user performs her daily activities is the STMicroelectronicLIS331 DLH 3-axis liner accelerometer. The device may also include oneor more electrodes and/or one or more light generating components (e.g.,an optical transmitter, such as a light-emitting diode (LED) or a laserdiode).

Additional sensors that can be used to measure at least one (e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, or 10) or more performance metrics and/or at leastone (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) or more characteristic of asubject's pelvic floor disorder (PFD) include, but are not limited to,pressure sensors, temperature sensors, pH sensors, and muscle qualitysensors. Exemplary muscle quality sensors are described in InternationalPublication No. WO2012149471A3, incorporated herein by reference in itsentirety. The additional sensor can be incorporated into the main bodyof the intravaginal device and/or within a tether (e.g., a flexible cordor ribbon) that can be optionally attached, e.g., by a removable orpermanent connection, to the main body of the intravaginal device.

A sensor of the invention may also be connected to a module or componentarranged within the intravaginal device that activates in response,e.g., to data collected by a sensor(s), at a predetermined time, e.g.,before, after, or during the performance of a PFL and/or PFR and/or adaily activity detected during daily monitoring. Recorded data from asensor(s) may, e.g., be run through a control circuit in theintravaginal device or in a peripheral device that recognizes thecharacteristic patterns of a pelvic floor movement and in turn controls(e.g., initiates) the activity of the module or component of theintravaginal device. For example, the control circuit may activate aheating element, an alert, or other activity based on the sensor data. Anon-limiting example of a control circuit that may be incorporated intoan intravaginal device of the invention is described in, e.g., Son etal. (Nature Nano. 9:397-404, 2014), which is incorporated herein byreference in its entirety. The control circuit may be present in aperipheral device (e.g., cell phone, watch, and tablet), which takes anaction based on the input data.

Electrical Impedance Myography (EIM) Technologies

The intravaginal device may be configured to utilize and includeelectrical impedance myography (EIM) technologies. The intravaginaldevice may contain an EIM sensor that can be used to measure acharacteristic during the performance of a pelvic floor lift and/orrelaxation. The EIM sensor may serve as the primary sensor or it mayfunction as an auxiliary sensor, e.g., in combination with a MEMSsensor. An EIM sensor measures electrical bioimpedance, i.e., the effectof tissue structure and properties (e.g., muscle fiber atrophy, musclefiber organization, deposition of fat and connective tissues, andinflammation) on the flow of an electrical current. To measureelectrical bioimpedance, an electrical current, e.g., a high-frequencyelectrical current and/or a multi-frequency electrical current, can beapplied to a tissue (e.g., pelvic floor tissues), e.g., by electrodes,and the resultant surface voltage patterns can be measured, e.g., byelectrodes, and analyzed. Generally, the voltage measured isproportional to tissue resistance (R).

In practice, there is a time shift, between the application of anelectrical current (sinusoid “a”) by an electrode and the generation ofthe measured voltage difference (sinusoid “b”), due to the inherent,capacitive nature of myocyte (e.g., muscle cell) membrane lipidbilayers. This capacitive nature of muscle cells allows the electricalcurrent (e.g., the charge) applied to a tissue to be stored and releasedout of phase with the applied electrical current, a process referred toas reactance (X). Reactance (X) and resistance (R) values may becombined to obtain the summary phase angle (θ) via the relationshipθ=arctan(X/R). The obtained phase angle (θ), reactance (X), andresistance (R) values may be used individually or in combination tomeasure a characteristic of the pelvic floor (e.g., the progression of,or resolution of, a pelvic floor disorder). For example, an increasedresistance (R) value may be obtained when a tested pelvic floor tissuecontains connective tissue, fat, and has a low level of muscle mass. Inanother example, a pelvic floor tissue experiencing muscle fiber atrophyand/or muscle fiber loss can result in a low reactance (X) value beingmeasured.

In particular instances, disease progression can be characterized by achange (e.g., an increase and/or a decrease) in the value of the phaseangle (θ), reactance (X), and/or resistance (R), as compared to areference (e.g., baseline) value. A reference value may be obtained,e.g., during the first use of the intravaginal device, such as during acalibration step. The reference values of the phase angle (θ), reactance(X), and/or resistance will depend on the status, e.g., health, of thepelvic floor tissues. In general, phase angle (θ) and reactance (X)values will decrease, as compared to the reference levels, as a pelvicfloor disorder characterized by the loss of muscle tone (e.g., musclefiber atrophy) advances. In particular instances, during treatment withan intravaginal device of the invention, an increase of about 5% or more(e.g., 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100%) in the phaseangle (θ) and/or the reactance (X) values, as compared to a referencevalue, may indicate an improved status (e.g., increased muscle quality)of the pelvic floor tissues. Furthermore, a decrease in the resistance(R) of about 5% or more (e.g., 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or100%), as compared to a reference value, may indicate an improved status(e.g., increased muscle quality) of the pelvic floor tissues.

Two additional aspects of EIM technologies are applicable to their usein the intravaginal device of the invention. The measured values ofphase angle (θ), reactance (X), and/or resistance (R) can be dependenton the frequency of the electrical current used to obtain EIM data.Thus, performing EIM measurements across a range of frequencies may helpto characterize tissue, e.g., by using an electrical current with afrequency and/or multiple frequencies (e.g., a high-frequencyalternating current) between about 1 kHz to about 10 MHz (e.g., 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300,400, 500, 600, 700, 800, 900, or 1000 kHz; or 1, 2, 3, 4, 5, 6, 7, 8, 9,10 MHz). Additionally, EIM data demonstrates electricalanisotropy-directional dependence of current flow, because electricalcurrent generally flows more easily parallel to the orientation ofmuscle fibers than perpendicular to the orientation of muscle fibers.Alterations in electrical anisotropy can also be used to measure acharacteristic of the pelvic floor muscles, e.g., to monitor theprogression of a pelvic floor disorder. For example, in pelvic floordisorders characterized by a loss of muscle tone (e.g., muscle fiberatrophy) a decrease in anisotropy, as compared to a reference level ofanisotropy, can indicate an improved status of the pelvic floor tissues(e.g., an increase in muscle quality). In some instances, the angle atwhich the EIM sensor contacts the vaginal tissues may be adjustable, tocollect data from multiple angles. In other embodiments, more than one(e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 20) EIM sensor is positioned tocontact vaginal tissues at varying angles, such an overall value forelectrical anisotropy within a pelvic floor tissue can be calculated.

In particular, the intravaginal device may be configured to deliver andto measure the effect of an electrical current (e.g., a high-frequencyalternating current) applied to the tissues (e.g., the musculature andnerves) of the pelvic floor. The EIM technology included in theintravaginal device can be used to determine at least one characteristicof a tissue of the pelvic floor, such as a characteristic selected fromthe group consisting of muscle quality and/or function, relativeforce-generating capacity, fat percentage, and/or status (e.g.,progression) of a pelvic floor disorder. Exemplary EIM sensors, such asa SKULPT® sensor, are described in International Publication Nos.WO2012149471A2, WO2015031278A1, and WO2016099824A; in U.S. PublicationNos. US20160038053A1 and US20160157749A1; and in U.S. Pat. Nos.8,892,198 and 9,113,808, which are incorporated herein by reference intheir entirety.

The intravaginal device may also include at least one electrode (e.g.,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 20 electrodes) configured to deliveran electrical current, such as a high-frequency alternating current, tothe tissues of the pelvic floor. Additionally, the intravaginal devicemay include at least one electrode (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,or 20 electrodes) configured to measure bioimpedance of the tissues ofthe pelvic floor. The delivery of an electrical current to and/or themeasurement of bioimpedance of the tissues of the pelvic floor can beachieved through the inclusion of at least one EIM sensor (e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, 10, or 20 EIM sensors), such as a SKULPT® sensor,in the intravaginal device. The electrode may be integrated with, andpart of, the bioimpedance sensor (e.g., an EIM sensor) or the electrodemay be a separate component. In particular embodiments, the intravaginaldevice includes at least one SKULPT® sensor (e.g., 1, 2, 3, 4, 5, 6, 7,8, 9, 10, or 20). The electrode(s), EIM sensor(s), and/or SKULPT®sensor(s) may be located within the main body and/or tether of theintravaginal device.

The sensors may be disposed along the tether and/or around the main body(e.g., a complete or incomplete ring form). A measure of bioimpedance ofthe vaginal canal could be computing using the characteristics of thevoltage signal measured by electrodes 915 and the current applied byanother electrodes 910. The bioimpedance could then be used to infercharacteristics of the tissue, including muscle quality and fat content.A measure of bioimpedance of the pelvic floor muscles could be computedusing the characteristics of the voltage signal measured by electrodes905 and the current applied by electrodes 900. The bioimpedance couldthen be used to infer characteristics of the tissue including musclequality and fat content.

The SKULPT® sensor(s) of the intravaginal device may also be connectedto a delivery module or component of the intravaginal device andconfigured to deliver a pharmaceutical agent to an individual user,e.g., in response to a measurement of muscle quality obtained by aSKULPT® sensor(s). Recorded data from a SKULPT® sensor(s) may, e.g., berun through a control circuit that recognizes the characteristicpatterns of a pelvic floor movement and/or a change in muscle qualityand in turn controls (e.g., initiates) the release of a pharmaceuticalagent from a delivery module (e.g., polymeric material, reservoir, orcoating) of the intravaginal device.

Light Detecting Sensors

The intravaginal device may also be configured to utilize and includesensing technologies based on light, e.g., laser or LED light, such aslight detection and ranging (LiDAR) sensors. In the art, LiDAR sensorshave been used for generating high-resolution maps, e.g.,three-dimensional (3D) maps of surfaces and objects, and for thetracking of an object's movements. In practice, LiDAR sensors measure,e.g., how far away each pixel in a 3D space is from the emitting device(e.g., an intravaginal device containing a LiDAR sensor), as well as thedirection to that pixel, which allows for the creation of a full 3Dmodel of the area around the sensor (e.g., the pelvic floor and vaginalcanal). A LiDAR sensor is configured to transmit a beam of light, andthen measure the returning signal when the light reflects off an object(e.g., the tissues of the pelvic floor and vaginal canal). The time thatthe reflected signal takes to return to the LiDAR sensor provides adirect measurement of the distance to the object (e.g., a tissuecomprising the pelvic floor and/or vaginal canal). Additionalinformation about the object, e.g., velocity or material composition,can also be determined by measuring certain properties of the reflectedsignal, such as the induced Doppler shift (e.g., a change in frequency).Finally, by steering the transmitted light and/or the incorporation ofmultiple LiDAR sensors, many different points of an environment can bemeasured to create a full 3D model. Exemplary LiDAR sensors aredescribed in, e.g., U.S. Publication No. US20150346340A1, incorporatedherein by reference in its entirety.

The intravaginal device may include at least one light detecting sensor,such as a LiDAR sensor (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 20 LiDARsensors), for example an on-chip LiDAR sensor. Inclusion of the LiDARsensor would allow the intravaginal device to collect mapping data,e.g., data on the size, shape, contour, structure, and/or texture of thepelvic floor and of the vaginal canal to generate a three-dimensional(3D) model of the pelvic floor tissues and vaginal canal. Additionally,one or more LiDAR sensors may be configured to measure a pelvic floorlift and/or relaxation. The intravaginal device may contain a LiDARsensor that is configured to measure the performance of a pelvic floorlift and/or relaxation. The LiDAR sensor may serve as the primary sensoror it may function as an auxiliary sensor. A LiDAR sensor may be locatedwithin the main body and/or tether of the intravaginal device. The datacollected from other sensors, for example can be integrated with the 3Dmodel to monitor the status (e.g., strength) of particular muscles ofthe pelvic floor during treatment with the intravaginal device. A lightgenerating component may be integrated with, and part of, the lightdetecting sensor (e.g., a LiDAR sensor) or the light generatingcomponent may be a separate component.

The light sensor(s) (e.g., a LiDAR sensor) of the intravaginal devicemay also be connected to a delivery module or component of theintravaginal device and configured to deliver a pharmaceutical agent toan individual user, e.g., in response to a measurement obtained by alight sensor(s) (e.g., a LiDAR sensor). Recorded data from a LiDARsensor(s) may, e.g., be run through a control circuit that recognizesthe characteristic patterns of a pelvic floor movement and in turncontrols (e.g., initiates) an alert to a user or the release of apharmaceutical agent from a delivery module (e.g., polymeric material,reservoir, or coating) of the intravaginal device.

Light sensors may also be used for pulse oximetry, which measures oxygensaturation.

Hormone and Toxin Sensors

The intravaginal device may also have a sensor that is capable ofdetecting, identifying, and/or measuring a molecule (e.g., a hormone, atoxin, a small molecule, a polynucleotide, and/or a polypeptide). Such asensor may be capable of detecting a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%,10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more change (e.g.,increase and/or decrease) in the level of a molecule (e.g., a hormone, atoxin, a small molecule, a polynucleotide, and/or a polypeptide) ascompared to a reference level obtained, e.g., during calibration with anintravaginal device of the invention and/or known in the art. The levelof a molecule (e.g., a hormone, a toxin, a small molecule, apolynucleotide, and/or a polypeptide) that may contribute to and/or beassociated with the onset and/or progression of a PFD and/or anotherdisease or condition, as described herein, is well known in the art.Non-limiting examples of such sensors are described in, e.g., U.S. Pat.No. 5,209,238 and in U.S. Publication No. US20090299156A1, which areeach incorporated herein by reference in their entirety.

Sensors for Detecting an Additional Biometric Parameter or Disease orCondition

The intravaginal device as described herein may also be configured withone or more additional sensors to detect an additional biometricparameter or disease or condition. For example, the intravaginal devicemay be configured with one or more accelerometers, gyroscopes,magnetometers, barometers, relative humidity sensors, bioimpedancesensors, thermometers, biopotential sensors, or optical sensors.Accelerometers (e.g., ADLX345 chip) may be used to track steps, gait,pelvic floor movement, activity, ballistocardiography, heart rate, heartrate volume, relative stroke volume, and respiration rate. A gyroscope(e.g., L3G4200D chip) may be used to track rotation and balance. Amagnetometer (e.g., MC5883L chip) may be used to performmagnetoencephalography by recording magnetic currents and electricalcircuits. A barometer (e.g., BMP085 chip) may be used to measurepressure. A relative humidity sensor (e.g., Si7023 chip) may be used tomeasure relative humidity. A bioimpedance sensor (e.g., AFE4300 chip)may be used to measure body composition and EIM. A thermometer (e.g.,BMP085 chip) may be used to measure temperature. A biopotential sensor(e.g., HM301D chip) may be used to measure electroencephalography (EEG),electromyography (EMG), echocardiography (EKG), heart rate, heart ratevolume, and pulse transit time (blood pressure). An optical sensor(e.g., MAX30100 chip) may be used to measure pulse oxygenation,photoplethysmogram, and blood pressure. A photoplethysmography sensor orelectrocardiogram (ECG) sensor may be used to track heart rate. A lightsensor may be used to measure pulse oximetry (e.g., blood oxygensaturation).

The intravaginal device described herein may use one or more of thefollowing sensors to acquire physiological data, including, but notlimited to, the physiological data outlined in Table 1 below. Allcombinations and permutations of physiological sensors and/orphysiological data are intended to fall within the scope of thisdisclosure.

TABLE 1 Physiological sensors and data Physiological SensorsPhysiological data acquired Optical Reflectometer Heart Rate, Heart RateVariability Example Sensors: SpO₂ (Saturation of Peripheral Lightemitter and receiver Oxygen) Multi or single LED and photo Respirationdiode arrangement Stress Wavelength tuned for specific Blood pressurephysiological signals Arterial Stiffness Synchronous detection/amplitudeBlood glucose levels modulation Blood volume Heart rate recovery Cardiachealth Motion Detector Activity level detection Example Sensors:Sitting/standing detection Inertial sensors, Gyroscopic sensors and/orFall detection Accelerometers GPS Skin Temperature Stress EMG(eletromyographic sensor) Muscle tension EKG or ECG(electrocardiographic sensor) Heart Rate Example Sensors: Heart RateVariability Single-lead ECG or EKG Heart Rate Recovery Dual-lead ECG orEKG Stress Cardiac health Magnetometer Activity level based on rotationLaser Doppler Power Meter Ultrasonic Sensor Blood flow Audio SensorHeart Rate Heart Rate Variability Heart Rate Recovery Laugh detectionRespiration Respiration type, e.g., snoring, breathing, breathingproblems (such as sleep apnea) User's voiceAny of the sensors described herein may collect physiological data,which can be transferred to and analyzed by, e.g., a peripheral device.This transformed data may then be presented on a graphical userinterface and/or may be provided to the user (or a health care provider)as an alert or notification on the peripheral device or on anotherdevice that indicates the nature of the physiological indicia.An Exchangeable, Separable, and/or Modular Tether

An intravaginal device of the invention may include an optional tetherand/or sleeve. A tether of the invention may include one or more tethermodules or separable tether portions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 20, 30, or more tether modules or separable tether portions). Eachtether module or separable tether portion may include a connector, e.g.,a flexible connector, by which multiple tether modules or separabletether portions may be connected, e.g., linked, to form a tether ofvarying length. A sleeve of the invention may be, e.g., a flexiblecover, that may be arranged to surround and encapsulate a tether (e.g.,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, or more tether modules orseparable tether portions). A sleeve of the invention may alternatively,or additionally, cover the main body of an intravaginal device of theinvention.

A tether or one or more tether modules or separable tether portionsand/or a sleeve may be configured with one or more sensors (e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 20, or more sensors), as described herein, andincluding at least one sensor selected from the group consisting of amovement sensor, accelerometer, gyroscope, micro-electro-mechanicalsystems (MEMS) sensor, G-sensor, tilt sensor, rotation sensor, a lightdetecting sensor, such as a light detecting and ranging (LiDAR) sensor,and electrical impedance myography (EIM) sensor, a pressure sensor, a pHsensor, a humidity sensor, a temperature sensor, a hormone sensor, amagnetometer, a barometer, a bioimpedance sensor, a thermometer, abiopotential sensor, an optical sensor, and/or a toxin sensor, and orany of the sensors described herein. A tether or one or more tethermodules or separable tether portions may be configured with one or moreenergy transmitters (e.g., RF transmitters).

Alternatively, or additionally, a tether or one or more tether modulesor separable tether portions and/or a sleeve may be configured todeliver one or more pharmaceutical agents (e.g., 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 20, or more pharmaceutical agents), as described herein. In someinstances, a tether or one or more tether modules or separable tetherportions and/or a sleeve may include one or more delivery modules orcomponents (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or more deliverymodules or components), such as those described herein and including aninner core, reservoir, coating layer, and/or gel.

In certain embodiments, the tether is configured as a separable tether,which may be a single separable piece of the tether or may be two ormore separable portions of the tether. The separable tether(s) can beconnected, for example, by a magnetic or interlocking connection. Thecontact point can also include an electrical connection that allowscommunication between the separable tether(s) and, e.g., a power supply(e.g., an AC power supply or a battery-powered supply). This may beuseful for applications where recharging the device is necessary or inorder to power the device during certain therapeutic applications.

Energy Transmitters

Energy transmitters 210, such as energy transmitters, lasers, orelectrical stimulation transmitters may be integrated into theintravaginal device. RF transmitters operate at frequencies, forexample, from 1 kHz to 100 MHz. The power level of RF transmitters mayvary from 1 mW to 500 W. RF transmitters emit energy in the form of heatand can be used to provide thermal energy to local tissue area of thevagina and vaginal canal that comes into contact with or is in proximityof the transmitters. RF transmitters may emit pulses of energy (e.g., in1-5 second bursts) or may emit energy for extended durations (e.g., 1-30minutes). RF transmitters may be powered wirelessly or by a wired powersource. The energy transmitters can communicate, e.g., via a wirelesscommunication (e.g., Bluetooth or Wi-Fi), such as with an antennaeand/or an authentication chip (e.g., for communicating with andtransmitting data to a peripheral device, such as a smart product, e.g.,tablets, computers, and smartphones (e.g., iPhone, iPads, and otherApple or Android computing devices).

Microcontrollers

A microcontroller (e.g., microcontroller unit (MCU)) is a small computer(e.g., a system on a chip (SOC)) that integrates all components of acomputer or other electronic system into a single chip (e.g., anintegrated circuit (IC) or microchip) and may contain a processor core,memory (e.g., non-transient storage), and programmable input/outputperipherals (e.g., sensors). The MCU can be used within an embeddedsystem, such as an intravaginal device, with a dedicated function, suchas monitoring the performance of pelvic floor exercises and providingbiofeedback. The MCU will typically contain a central processing unit(CPU) (e.g., a 4-bit to 64-bit processing unit, e.g., a 4-bit, a 32-bit,or a 64-bit processor), volatile memory (RAM) for data storage,operating parameter storage (e.g., ROM, EPROM, EEPROM, and/or Flashmemory), discrete input and output pins (e.g., general purposeinput/output pins (GPIO), serial input/output pins (e.g., universalasynchronous receiver/transmitter (UARTS), e.g., serial input/outputpins for communication standards such as TIA (formerly EIA) RS-232,RS-422, and/or RS-485), other serial communication interfaces (e.g.,Inter-Integrated Circuit (I²C), Serial Peripheral Interface (SPI),Universal Serial Bus (USB), and Ethernet), peripherals, clock generator,converters (e.g., analog-to-digital and/or digital-to-analogconverters), and in-circuit programming (ICSP) and/or in-circuitdebugging (ICD) support.

Microcontrollers can contain at least one (e.g., 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 800, 80, 100, 150, or more)general purpose input and/or output pins (GPIO). GPIO pins are softwareconfigurable to either an input or an output state. GPIO pins configuredto an input state are used to read sensors (e.g., movement,acceleration, rotation, pH, and/or muscle quality sensors) or otherexternal signals. GPIO pins configured to the output state can drive anexternal device, such as a device capable of providing biofeedback(e.g., LEDs, motors).

An exemplary microcontroller useful in the featured invention is theTexas Instruments® MSP430F5438A, however other suitable microcontrollersmay be used. This can be used to control the sensors, energytransmitters, and route power to any components within the intravaginaldevice.

The microcontroller (e.g., in the peripheral device and/or theintravaginal device) may also be configured to implement an algorithm todetect pelvic floor movement (e.g., pelvic floor lift, pelvic floorrelaxation, Valsalva maneuver, sustained pelvic floor lift, and seriallyrepeated pelvic floor lift) or other indicia relevant to a health stateof a subject. The microcontroller may collect data (e.g., position andangle data) from sensors (e.g., MEMS accelerometers), process andtransform the data using the predetermined algorithm, and output newdata to the user, e.g., on a user interface or peripheral device. Forexample, the microcontroller may collect sensor angle data, and from thedata, determine whether a pelvic floor movement is performed correctly.Furthermore, an algorithm performed by a processor may be used, e.g., toquantify the duration, number, and quality of pelvic floor movementsperformed by the user or other indicia relevant to a health state of thesubject. The microcontroller may be configured with the algorithm toalert the user, e.g., by providing indicia obtained from the sensors ofthe intravaginal device, such as whether the exercise(s) are beingperformed properly or improperly and/or whether the vital signs of theuser indicate an adverse health state. The microcontroller may performthe computations, which can be stored using, e.g., a non-transitorystorage medium. The microcontroller or processor may only be in theperipheral device, and not the intravaginal device. The microcontrollermay be configured to enable communication between the intravaginaldevice and a peripheral device. The microcontroller or peripheral devicemay be programmed with software or hardware that transforms the dataobtained from the sensors on the intravaginal device, the results ofwhich may then be stored in the device (e.g., using a non-transitorystorage medium), and provides the transformed data to a user, e.g., on auser interface.

A microcontroller or processor may be controlled by computer-executableinstructions stored in memory (e.g., non-transitory storage medium) soas to provide functionality, such as is described herein. Suchfunctionality may be provided in the form of an electrical circuit. Inyet other implementations, such functionality may be provided by aprocessor or processors controlled by computer-executable instructionsstored in a memory coupled with one or more specially-designedelectrical circuits. Various examples of hardware that may be used toimplement the concepts described herein include, but are not limited to,application specific integrated circuits (ASICs), field-programmablegate arrays (FPGAs), and general-purpose microprocessors coupled withmemory that stores executable instructions for controlling thegeneral-purpose microprocessors.

Transmitter and Receiver

A transmitter and receiver may be positioned within the intravaginaldevice and/or in the peripheral device, along with any additionalcomponents required to enable wireless communication (e.g., Bluetooth,Wi-Fi, and/or RF), such as an antennae and/or an authentication chip(e.g., for communicating with Apple products, e.g., iPhone, iPads, andother Apple computing devices). For example, Bluetooth communication canbe performed by Roving Network's RN42APL-I/RM microchip. Forauthentication, for example, an Apple Authentication Chip 2.0C can beused to connect to the RN42APL-I/RM microchip via I²C and allow theintravaginal device to communicate with Apple products. One example ofan Apple chip is the iPod Authentication Coprocessor, with part numberP/N MF1337S3959. The transmitter and receiver may also be housed in anexternal box and connected to the intravaginal device by a detachablecable.

Power Source

The power source may be a battery located within the intravaginal device(e.g., an internal battery) and can be connected to the electroniccomponents that it will power (e.g., sensor(s), microcontroller,transmitter and receiver, RF transmitter, and sensory outputcomponent(s)) by either a circuit board (e.g., a flexible circuit board)or a wire. The intravaginal device can include an ON/OFF switch (e.g., abutton), that can be activated, e.g., prior or post insertion of theintravaginal device, by the individual. The power state of theintravaginal device can be indicated to the individual, e.g., by a light(e.g., an LED), a vibration, and/or by a notification displayed on theuser interface of the electronic device, e.g., via an accompanyingsoftware application). The internal battery may be rechargeable and/orreplaceable, such as a nickel-cadmium battery or a lithium ion battery.The intravaginal device may be configured to allow for the battery to becharged by a charging cradle (e.g., a charging case), a detachablecable, and/or by inductive wireless charging technology.

In some instances, the internal battery has a sufficient charge to powerthe intravaginal device for an entire treatment period (e.g., about oneday to about three years (e.g., about three to six weeks (e.g., at leastone week) or three to six months)). The internal battery can beconfigured to modulate its power output level based on the usage stateof the intravaginal device, e.g., by entering a lower-power state whenthe intravaginal device is not being used to measure a pelvic floormuscle movement (e.g., a pelvic floor lift (PFL) and/or a pelvic floorrelaxation (PFR)). The usage state may be detected automatically by theintravaginal device, or be communicated to the intravaginal device bythe electronic device and user interface, e.g., by the individualbeginning a training session using the accompanying softwareapplication. The ON/OFF switch may also be configured to communicate tothe intravaginal device when a training session will begin and therebymodulate the power state of the device. For example, the ON/OFF switchcan be configured to respond to one long press (e.g., a 5-15 secondpress and hold) by turning on, while one short press (e.g., a 1-3 secondpress and hold) can cycle the intravaginal device into a training stateduring which sensor data can be collected, and a second short press(e.g., one 1-3 second press and hold) or a double press (e.g., two 1-3second press and holds) can end a training session and place theintravaginal device into a power-saving (e.g., low-power) state.

In some instances, the power source is a battery located in a separatehousing (e.g., an external battery) and connected to the intravaginaldevice, e.g., by a detachable cable. For example, power may be suppliedthrough two replaceable and/or rechargeable AA batteries (e.g., 1.5Vbatteries). In some instances, the power is provided by a power cordthat connects to, for example, a power box (e.g., an external battery)or AC outlet.

Materials

The intravaginal device (e.g., main body (e.g., the substantially ringshaped form) sleeve, and/or tether) may be fabricated from a variety ofbiocompatible materials. For example, silicone, polyethylene,polypropylene, polystyrene, polyester, polycarbonate, polyvinylchloride, polyethersulfone, polyacrylate, hydrogel, polysulfone,polyetheretherketone, thermoplastic elastomers, poly-p-xylylene,fluoropolymers, rubber, and latex are suitable materials from which tofabricate the intravaginal device. Additionally, the intravaginal device(e.g., main body (e.g., the substantially ring shaped form) and/ortether) may be fabricated from or include components fabricated frommetals and/or plastics. For example, the intravaginal device may containa flexible spring, wire, or core structure (e.g., for providing tension,e.g., pushing against the vaginal walls of the individual to positionand orient the intravaginal device at a location proximal to theindividual's cervix or vaginal cuff) made from metal and/or plastic. Thematerials from which the intravaginal device is fabricated may beflexible or inflexible. In some instances, the intravaginal device(e.g., main body (e.g., the substantially ring shaped form) and/ortether) contains both flexible and inflexible materials.

When configured for delivery of a pharmaceutical agent the material ofthe intravaginal device (e.g., materials of the main body, tether,and/or a delivery module) may comprise a biocompatible polymericmaterial, e.g., that is permeable to the passage of the pharmaceuticalagent. Acceptable polymeric materials include those that may release apharmaceutical agent, e.g., by diffusion or through micropores or holes.The polymeric material may comprise, e.g., a thermoplastic polymer, suchas a silicone elastomer, a polysiloxane, a polyurethane, a polyethylene,a polyethylene vinyl acetate (PEVA), ethylene-vinyl acetate (EVA), acellulose, a polystyrene, a polyacrylate, a polyamide, and/or apolyester polymer. An EVA material may be useful due to its mechanicaland physical properties (e.g., solubility of the drug in the material).The EVA material may be any commercially available ethylene-vinylacetate copolymer, such as ELVAX®, EVATANE®, LUPOLEN®, MOVRITON®,ULTRATHENE®, ATEVA®, and VESTYPAR®. Additional non-limiting examples ofmaterials useful in the manufacture of an intravaginal device configuredfor delivery of a pharmaceutical agent are described in, e.g., Malcolmet al. (Int. J. Women. Health. 4:595-605, 2012), U.S. Publication No.US20090004246A1, and U.S. Pat. Nos. 3,545,439, 4,822,616, 4,292,965,8,858,977, 7,829,112, 4,215,691, 4,155,991, 7,910,126, and 4,012,496,each of which are herein incorporated by reference in their entirety.

Coatings

The intravaginal device (e.g., main body (e.g., the substantially ringshaped form), sleeve, and/or tether) may be coated with a substance,such as a biomaterial, to improve a property of the device, such as,e.g., adhesion of the intravaginal device to the tissue of the vaginalcanal (e.g., the vaginal walls and/or the cervix). The biomaterial maybe a biocompatible adhesive, such as a hydrogel e.g., hyaluronic acid(HA) or a derivative thereof. Optimally, the biomaterial is abiodegradable material. Additionally, the biomaterial may be formulatedsuch that it performs its desired function (e.g., adhesion) for apredictable period of time (e.g., a time corresponding to the treatmentperiod for an individual). The intravaginal device may also be coatedwith a lubricant, e.g., to ease insertion or removal of the device fromthe vagina.

The intravaginal device (e.g., the main body, tether, including tethermodule(s), and/or sleeve) may also have a coating, a layer, and/or a gel(e.g., on a surface of the device, such as an exterior surface)containing at least one pharmaceutical agent (e.g., 1, 2, 3, 4, 5, ormore pharmaceutical agents) useful in the treatment of a PFD or thesymptoms thereof (e.g., changes to muscle tone, changes to musclestrength, bladder leakage, anal or fecal leakage, pain, frequency, andurgency), or another disease or condition affecting a female subject,e.g., as described herein. For example, the device may be coated with alayer comprising a pharmaceutical agent either completely or partially.Such a coating may be a temperature-sensitive material, such as wax,that melts at the body temperature. Alternatively, the coating maycomprise a biodegradable polymer designed to allow pharmaceutical agentrelease by bulk or surface erosion and include natural and syntheticpolymers alone or in combination with other materials, for example,polysaccharides (e.g., alginate, dextran, cellulose, collagen, andchemical derivatives thereof), proteins (e.g., albumin and gelatin andcopolymers and blends thereof), polyhydroxy acids (e.g., polylactides,polyglycolides, polyethylene terephthalate, polybutyric acid,polyvaleric acid, polylactide-co-caprolactone, polyanhydrides,polyorthoesters, and blends and co-polymers thereof). The coating mayalso comprise a non-degradable polymer (e.g., polyamides, polyethylene,polypropylene, polystyrene, polyvinyl chloride, polymethacrylic acid,and derivatives thereof), or any other suitable coating material thatcoats all or at least a portion of the device.

Physical and chemical properties of the coatings can be tailored tooptimize their intended use, such as controlling the rate of release ofthe pharmaceutical agent incorporated therein. Pharmaceutical agentrelease from the coating can occur, e.g., by diffusion or erosion, or bya combination of both, leading to immediate or controlled, rapid, slow,continuous, or pulsed delivery of the pharmaceutical agent to and/orthrough the vaginal tissue. The rate of agent release may be affected bythe physicochemical properties of the agent, the composition of thecoating, and/or on the surrounding media at the site of administration.

Non-limiting examples of coatings useful in the manufacture of anintravaginal device configured for delivery of a pharmaceutical agentare described in, e.g., U.S. Publication No. US20050276836A1 and U.S.Pat. No. 4,292,965, which are herein incorporated by reference in theirentirety.

A Tool for Insertion of the Intravaginal Device

The intravaginal device may be inserted with an insertion tool (see,e.g., International Publication No. WO2018023037, the disclosure ofwhich is hereby incorporated in its entirety). The insertion tool maydeform (e.g., bend, twist, compress, pull, and/or shape) and hold theintravaginal device in such a way that it can be deployed from theinsertion tool at an appropriate location (e.g., a location proximal tothe cervix or vaginal cuff of an individual) and in an appropriateorientation (e.g., a position that allows for optimal sensormeasurements to be obtained) within an individual. The insertion toolmay comprise a device housing configured to hold and shape theintravaginal device, and a plunger configured to apply the necessaryforce to push the intravaginal device from the device housing an deploythe intravaginal device inside the individual. The insertion tool can beconfigured for use with or coated with a lubricant to ease the insertionprocess. Insertion tool 400 contains an elongated shaft applicator,which houses intravaginal device 100. Insertion tool 400 may alsocontain upper portion 610 and lower portion 620, which may be joinednear the distal end by hinge 630. Upper portion 610 and lower portion620 may clasp the intravaginal device 100 before insertion into thevagina. After insertion, the ends of upper portion 610 and lower portion620 may be pressed to release the device while removing insertion tool400, leaving intravaginal device 100 in place inside the vagina. Theinsertion tool or applicator may be disposable or may be reused, e.g.,after cleaning by methods known in the field (e.g., water and soap orother hygienic or sterilization methods). As the main body of theintravaginal device can have a diameter of about 20 mm to about 80 mmand a thickness of about 0.1 mm to about 1 mm, and the tether can have alength of about 14 cm or less and a width of about 1 to about 10 mm, theinsertion tool may be configured to comprise slightly larger dimensionssuch that it can enclose or deform the device. The X dimension may be,e.g., from about 0.2 mm (about twice the thickness of the ring) to about100 mm (slightly larger than the diameter of the ring when notdeformed), the Y dimension may be e.g., from about 0.1 mm to about 50mm, and the Z dimension may be e.g., from about 0.2 mm to about 115 mm.

A Database

A database may be located on a local electronic device (e.g., aperipheral device, such as a computer, phone, or tablet) or on a remoteelectronic device that can communicate via the internet (e.g., aweb-located and/or cloud-based database). The database can be a centraldatabase that collects, stores, and performs calculations with thesensor data collected from an intravaginal device used by an individual.Sensor data and additional data provided by an individual (e.g.,information provided by an individual on symptoms of a pelvic floordisorder that they have experienced, e.g., answers to a questionnaire)may be communicated to (e.g., uploaded to) or stored in the database ona periodic basis upon transmission from the intravaginal device. In someinstances, communication with the database is substantially continuous(e.g., upload of data occurs in substantially real-time during theperformance of a pelvic floor exercise). In other instances,communication with the database occurs on an hourly or daily basis(e.g., at least one per hour and/or at least once per day) or wheninitiated by the user. The database can be reviewed by the user aftertreatment to assess the progress. The data could also been transmittedto the healthcare provider (e.g., automatically, by a third party, or bythe user).

A User Interface

The user interface may comprise a software application configured toprovide an interactive display to an individual of her (i) present,daily, weekly, monthly, and overall training progress with anintravaginal device of the invention and/or (ii) present, daily, weekly,monthly, and overall health status of her urogenital system and/orpelvic floor (e.g., the muscle fibers of the levator ani, e.g., thepubococcygeus, ileococcygeus, coccygeus, puborectalis muscles andassociated connective tissues). In particular, the application isdesigned to guide, coach and motivate a user through positioning (e.g.,orienting) the intravaginal device within her vagina (e.g., proximal tothe cervix or vaginal cuff) and completing a training program includingthe performance of pelvic floor lifts (PFLs) and/or pelvic floorrelaxations (PFRs). The application provides a step-by-step guide andreal-time feedback (e.g., corrective instruction) on positioning theintravaginal device within the vagina and on the specific movements(e.g., pelvic floor muscle engagement and relaxation) which comprise aPFL and/or PFR.

The application may also provide feedback to an individual on how theperformance of an everyday movement or activity (e.g., an index event)affects the health status of her urogenital system and/or pelvic floor(e.g., feedback based on data produced by one or more of the sensors inthe device). The feedback provided by the application may be reviewed bythe individual and/or a medical practitioner and/or a third party insubstantially real-time or the feedback may be stored by theapplication, e.g., in the memory of the intravaginal device, a connectedelectronic device (e.g., a computer, tablet, and/or smartphone), or adatabase (e.g., a local database or a remote database, such as aninternet-based database).

The application can include several screens: Welcome and/or Login,Calibration and Orientation, Dashboard, Training and Coaching, LiveMode, Menu, Introduction, Device, Exercise History, and Symptoms.

On first use of the application, the Welcome and/or Login screen canallow a user to establish a training account on the database where theuser's training data (e.g., sensor data) will be stored. This step caninclude the registration of her intravaginal device and the creation ofa username and password. The user can also elected to connect with ahealthcare professional, who is overseeing her training, with whom theywill share her training data.

The user may also be prompted to insert and calibrate her intravaginaldevice using the Calibration and Orientation screen. The Calibration andOrientation screen will coach the user through inserting and orientingthe intravaginal device. The application may show the user a schematicdiagram of the intravaginal device and prompt the user to identify theindicia on her own device that marks the device's top and front sides.The user may be asked to insert the device by hand or by using theinsertion tool, such that the top indicia will be facing the top of thevagina and the front indicia will be facing the user's anterior. Inreal-time the application can provide the orientation of theintravaginal device on its x, y, and z-axis during the insertion stepand will coach the user to orient the device parallel to the top of thevaginal canal and proximal to the cervix or vaginal cuff. When thecorrect orientation is obtained, the application can prompt the user toconfirm that the indicia marking the front (e.g., anterior) side of theintravaginal device is facing the anterior side of her body. Thisorientation step could be conducted on insertion of the device. If thedevice is removed and subsequently replaced the orientation step may berepeated. Next, the application can coach the individual throughperforming a series of exercises, such as pelvic floor lifts (PFLs) andpelvic floor relaxations (PFRs), to establish a baseline of measurementsfrom which the progress of the user of the intravaginal device can bedetermined over time. The calibration step can be repeated at any timechosen by the user.

The application may also include a Dashboard screen displaying the totalpower charge of the intravaginal device substantially in real-time, thetotal time the intravaginal device has been in place inside the user,the total number of PFLs and PFRs performed on a given day, a pHmeasurement (e.g., a pH measurement taken substantially in real-timeand/or an average pH measurement for a given day and/or hour), a scorerelated to the pelvic floor muscle quality of the user, and at least onescore related to the overall progress of the user during the treatmentperiod. The Dashboard may also provide a summary of data collectedduring the use of the optional Live Mode, which can be used forsubstantially real-time monitoring of the overall health status of auser's urogenital system and/or pelvic floor (e.g., the muscle fibers ofthe levator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues). The Dashboardmay provide the total number of PFLs and PFRs that were performed, e.g.,intentionally or unintentionally, by a user as they performed her dailyactivities, and a score related to the amount of stress that has beenplaced on the pelvic floor muscles during a time period in which LiveMode was active.

The overall progress score of the user can be calculated based on a setof baseline measurements obtained during the calibration session. Thedata collected during the calibration session can include, but is notlimited to, maximum number of PFLs and/or PFRs performed until pelvicfloor muscle exhaustion is reached (e.g., the user can no longer performPFL and/or a PFR), maximum change in distance from the insertionposition of the intravaginal device during a PFL and a PFR, ameasurement of muscle quality and/or strength, and a pH measurement.During the calibration step, if a light detecting sensor, such as aLiDAR sensor, is included in the intravaginal device, reference (e.g.,baseline) measurements can be collected on the three-dimensional (3D)structure of the pelvic floor and vaginal tissues, such that an initial(e.g., reference) 3D model of the user's pelvic floor and vaginaltissues can be generated. Additionally, if an electrical impedancemyography (EIM) sensor is included in the intravaginal device, reference(e.g., baseline) values of the phase angle (θ), reactance (X), and/orresistance (R) can be obtained. The EIM reference levels measured by theintravaginal device may be used to calculate a reference score, e.g., areference muscle quality score, which may be displayed to the user. Areference muscle quality score may be assigned to a particular muscleand/or tissue of the pelvic floor, or to the pelvic floor as a whole(e.g., an overall reference muscle quality score). An additionalcomponent of the calibration step may include the completion of aquestionnaire designed to assign a symptom score reflective of theseverity of the user's PFD. Additionally, if a hormone sensor isincluded in the intravaginal device, reference (e.g., baseline) valuesfor at least one reproductive hormone (e.g., gonadotropin-releasinghormone (GnRH), follicle-stimulating hormone (FSH), lutenizing hormone(LH), estrogen, progesterone, human chorionic gonadotropin (HCG) andderivatives thereof) can be obtained. If a toxin sensor is included inthe intravaginal device, a reference (e.g., baseline) values for a toxin(e.g., a bacterial toxin, a fungal toxin, a viral toxin, and/or a toxinproduced by a parasite) may be compared to a predetermined level, suchas a level known in the art or set by a medical practitioner. An overallprogress score can be calculated from the calibration measurements aloneor from the calibration measurements and the symptom score together. Ascore related to the overall health status of a user's urogenital systemand/or pelvic floor may also be generated. Alternatively, the symptomscore may also be displayed on the Dashboard.

If the device includes an EIM sensor, such as a SKULPT® sensor, a score(e.g., a muscle quality score) related to a user's phase angle (θ),reactance (X), and/or resistance (R) values, as compared to a referencelevel, can be displayed by the application on the user interface.Depending on the arrangement of the EIM sensors within the intravaginaldevice, particular muscles of the pelvic floor may be specificallyidentified with a muscle quality score. In some instances, an overallmuscle quality score for the pelvic floor can be calculated.

If the device includes a light detecting sensor, such as a LiDAR sensor,the application may also display to the user on the user interface a 3Dmodel of her pelvic floor and vaginal tissues. Specific scoring data(e.g., a muscle quality score), such as may be calculated from datacollected by other sensors within the intravaginal device (e.g., amovement sensor, accelerometer, gyroscope, micro-electro-mechanicalsystems (MEMS) sensor, G-sensor, tilt sensor, and rotation sensor, EIMsensor, pressure sensor, muscle quality sensor, and/or pH sensor), canbe displayed overlaid onto the 3D model to identify particular regionsof the pelvic floor that need additional training (e.g., strengtheningand/or relaxing). A 3D model of the patient's vaginal canal and pelvicfloor tissues can be generated at any time during the treatment periodand/or be generated substantially continuously.

The Dashboard display on the user interface can include an operativebutton for launching a Training and Coaching screen. The Training andCoaching screen can provide the user with real-time visual feedback onher performance of a PFL and/or a PFR. For example, the user can becoached through the performance of a particular series of PFLs and/orPFRs, such as a series including performing PFLs and/or PFRs over a settime interval (e.g., 1-5 minutes, 1-60 seconds, or 15 seconds) and a settime interval of rest (e.g., 1-5 minutes, 1-60 seconds, or 15 seconds).The user can be instructed to repeat the series one or more (e.g., 1, 2,3, 4, or 5) times. A graph can be generated to indicate the strength ofeach PFL and/or a PFR performed by the user.

The Dashboard display on the user interface can include an operativebutton for launching a Live Mode screen. The Live Mode screen maypresent the user with the option of activating Live Mode (e.g.,real-time monitoring) and allow the user to establish a preferencesetting that determines which sensors are actively collecting dataduring Live Mode and how feedback should be displayed to the user. TheDashboard may provide a summary of the information collected by thesensors in Live Mode.

The Introduction screen displayed by the application on the userinterface provides educational material on PFDs and an explanation ofhow the intravaginal device can be used to treat PFDs. The Device screendisplayed by the application on the user interface provides specificinformation on a user's intravaginal device. For example, this screencan provide information on the battery level (e.g., charge) of theintravaginal device and how long (e.g., how many days) the intravaginaldevice has been inside the user. The Exercise History screen displayedby the application on the user interface provides information on pasttraining sessions performed by the user. The Symptoms screen displayedby the application on the user interface provides information for a userto track the symptoms of a PFD that they are experiencing on a givenday, such as a form-based questionnaire (e.g., an optional daily surveyand/or diary). The Menu screen displayed by the application on the userinterface provides easy navigation to all other screens included in thesoftware application.

The user interface may also include a function that allows the user toview charts showing her progress during treatment and during dailymonitoring. The data shown using this charting function can betransmitted by the user to her healthcare provider or to a third party(e.g., automatically or by the user).

The user interface may also include a function to control the RFtransmitters to deliver energy. For example, the power, frequency, andduration of energy transmission may be modulated by the user interfacebased on user preferences and physician recommendations. Theintravaginal device may have temperature sensors that sense thetemperature changes as a result of the RF transmitters. Upon sensing atemperature that is too high, it may communicate with the user interfaceto alert the user to lower the power, frequency, and/or duration of RFtreatments. The device may also automatically turn the RF emitters up ordown in response to a predetermined temperature threshold being or notbeing crossed.

The user interface may also present the user with a presentation ofother vital signs based on sensor data. The intravaginal device asdescribed herein may also be configured with one or more additionalsensors to detect an additional biometric parameter or disease orcondition. For example, any one of the accelerometers, gyroscopes,magnetometers, barometers, relative humidity sensors, bioimpedancesensors, thermometers, biopotential sensors, or optical sensors mayprovide indicia to the user regarding steps, gait, pelvic floormovement, activity, ballistocardiography, heart rate, heart rate volume,relative stroke volume, respiration rate, rotation, balance, magneticcurrents, electrical circuits, pressure, relative humidity, bodycomposition, temperature, heart rate, heart rate volume, and pulsetransit time, blood pressure, pulse oxygenation, and pulse oximetry(e.g., blood oxygen saturation).

III. Pelvic Floor Disorders (PFDs) that can be Treated with theIntravaginal Device

Pelvic floor disorders (PFDs) that can be treated by the intravaginaldevice and the methods described herein include a wide range ofconditions that occur when the muscles of the pelvic floor (PF) are weak(e.g., hypotonic), tight (e.g., hypertonic), or there is an impairmentof or damage of the sacroiliac joint, lower back, coccyx, or hip joints.Neurogenic factors, including lumbosacral nerve damage, such as thenerve damage seen in multiple sclerosis and stroke patients, can alsocontribute to the development and progression of PFDs (National ClinicalGuideline Centre (UK). NICE Clinical Guidelines. 148, 2012). Pelvicsurgery (e.g., hysterectomy), vaginal childbirth, age, obesity,diabetes, connective tissue disorders, and genetic predisposition havealso been identified as risk factors for the development of PFDs (Memonet al., Womens Health (Lond. Engl.). 9(3), 2013).

Symptoms of PFDs include changes to muscle tone, changes to musclestrength, bladder leakage, anal or fecal leakage, pain, frequency, andurgency. Exemplary PFDs include, but are not limited to, urinaryincontinence (UI), stress urinary incontinence (SUI), urge incontinence,mixed stress and urge urinary incontinence, dysuria (e.g., painfulurination), anal or fecal incontinence, pelvic organ prolapse (POP)(e.g., urethra prolapse (urethrocele), bladder prolapse (cystocele), orboth urethra and bladder prolapse (cystourethrocele), vaginal vault andcervix prolapse (vaginal vault prolapse), uterus prolapse (uterineprolapse), rectum prolapse (rectocele), sigmoid colon prolapse(sigmoidocele), and small bowel prolapse (enterocele)), pelvic pain,sexual dysfunction (e.g., coital incontinence, a sexual pain disorder,dyspareunia, vaginismus, and/or impaired sexual arousal), weak orimpaired pelvic floor muscle function, post-labor issues or damage, painand/or incontinence caused by damage to a lumbosacral nerve, andnonrelaxing pelvic floor dysfunction.

a. Incontinence

Forms of urinary and anal or fecal incontinence that can be treated bypelvic floor muscle training (e.g., by the performance of a pelvic floorlift (PFL) using, e.g., the device and methods described herein include,but are not limited to, urinary incontinence (UI), stress urinaryincontinence (SUI), urge incontinence, mixed stress and urge urinaryincontinence, and anal or fecal incontinence.

The urethra is the canal leading from the bladder that discharges urineexternally. In females, the urethra is a ˜4 cm canal passing from thebladder, in close relation with the anterior wall of the vagina andhaving a long axis that parallels that of the vagina opening in thevestibule of the vagina posterior to the clitoris and anterior to thevaginal orifice. (See STEDMAN's MEDICAL DICTIONARY, at page 2072(28^(th) edition, 2005). The urinary bladder refers to amusculomembranous elastic bag serving as a storage place for the urine,filled via the ureters and drained via the urethra. The bladder neck isthe smooth muscle of the bladder, which is distinct from the detrusormuscle. In females, the bladder neck consists of morphologicallydistinct smooth muscle. The large diameter fasciculi extend obliquely orlongitudinally into the urethral wall. In a normal female, the bladderneck above the pelvic floor is supported predominantly by thepubovesical ligaments, the endopelvic fascia of the pelvic floor, andlevator ani. These support the urethra at rest; with elevatedintra-abdominal pressure, the levators contract increasing urethralclosure pressure to maintain continence. This anatomical arrangementcommonly alters after parturition and with increasing age, such that thebladder neck lies beneath the pelvic floor, particularly when theintra-abdominal pressure rises. This mechanism may fail to maintaincontinence, leading to incontinence as a result of urethralhypermobility, whereas a normal woman has no issues with any urinary oranal or fecal leakage.

Exercise using an intravaginal device of the invention, as describedherein, can be used to strengthen the pelvic floor muscles, which canrestore an anatomical arrangement that promotes continence.

b. Organ Prolapse

Pelvic organ prolapse (POP) that can be treated by pelvic floor muscletraining (e.g., by the performance of a pelvic floor lift (PFL) and/or apelvic floor relaxation (PFR)) using, e.g., the device and methodsdescribed herein include, but are not limited to, urethra (urethrocele),bladder (cystocele), or both urethra and bladder (cystourethrocele),vaginal vault and cervix (vaginal vault prolapse), uterus (uterineprolapse), rectum (rectocele), sigmoid colon (sigmoidocele), and smallbowel (enterocele) prolapse. A detailed description of pelvic organprolapse can be found at(www.acog.org/Resources-And-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Pelvic-Organ-Prolapse),which is hereby incorporated by reference. A standardization of theterminology associated with POP is described in Bump et al. American J.Obstet. Gynec. 175.1 (1996): 10-17, which is hereby incorporated byreference.

In general, the various stages of POP are based on the maximal extent ofprolapse relative to the hymen, in one or more compartments. A normalpatient is considered stage 0 while stage I (least severe) to stage IV(most severe) are quantified by the distance of the prolapse as follows:

Stage 0: No prolapse; anterior and posterior points are all −3 cm.

Stage I: The criteria for stage 0 are not met, but the most distalportion of the prolapse is >1 cm above the level of the hymen.

Stage II: The most distal portion of the prolapse is ≤1 cm proximal toor distal to the plane of the hymen.

Stage III: The most distal portion of the prolapse is >1 cm below theplane of the hymen but protrudes no further than 2 cm less than thetotal vaginal length in cm.

Stage IV: Essentially, complete eversion of the total length of thelower genital tract is demonstrated. The distal portion of the prolapseprotrudes to at least 2 cm. In most instances, the leading edge of stageIV prolapse will be the cervix or vaginal cuff scar.

A device of the invention may detect hypermobility of a woman's pelvicfloor muscles (e.g., a woman with stage I, II, III, or IV POP (such asmild to severely symptomatic patients)). For example, sinusoidal-typecurvature of the device may occur upon performing a lift exercise,suggesting that the musculature of the pelvic floor is too weak toconstrain the device in a linear fashion. A woman with stage IV, ortotal prolapse, exhibits pelvic floor collapse and the inability to“raise” the device of the invention during a PFL exercise. Additionally,the device may be completely extruded from the vagina or urethra.

Other routine activities may increase abdominal pressure and causepelvic floor damage. Examples of activities that can cause pelvic floordamage include, for example weightlifting (e.g., deadlifts, CrossFit®training), lifting heavy objects (e.g., children), running, chroniccoughing, childbirth, and constipation. These activities can bemonitored during use of an intravaginal device of the invention and theuser can receive a signal warning them that the activities maynegatively affect their pelvic floor health.

c. Sexual Dysfunction

Sexual dysfunction that can be treated by pelvic floor muscle training(e.g., by the performance of a pelvic floor relaxation (PFR)) using,e.g., the device and methods described herein, can be divided into twobasic groups: (1) individuals with damage or weakness in a muscle of thepelvic floor (PF) (e.g., individuals having pelvic floor musclehypotonus), and (2) individuals having high pelvic floor muscle tone(e.g., high contraction), pelvic floor muscle spasm, and/or pain (e.g.,individuals having pelvic floor muscle hypertonus) (Rogers. Can. Urol.Assoc. J. 7:S199-S201, 2013; Bozkurt et al. Taiwanese Journal ofObstetrics & Gynecology. 53:452-458, 2014; Rosenbaum. J. Sexual Med.4(1):4-13, 2007). Group 1 individuals may include, for example,individuals having urinary and/or anal or fecal incontinence, pelvicorgan prolapse (POP), and coital incontinence. Group 2 individuals mayinclude, for example, individuals having coital incontinence, a sexualpain disorder, dyspareunia, vaginismus, and/or impaired sexual arousal.

d. Neurological Disease or Injury

Pelvic floor disorders (PFDs) that can be treated by pelvic floor muscletraining (e.g., by the performance of a pelvic floor lift (PFL) and/or apelvic floor relaxation (PFR)) using e.g., the device and methodsdescribed herein, may occur in individuals experiencing neurologicaldisease or injury, such as brain conditions, suprasacral spinal cordconditions, and sacral spinal cord or peripheral nerve conditions. Forexample, multiple sclerosis (MS) or stroke patients commonly experiencea PFD and present with a variety of symptoms including urgency, urgeincontinence, daytime frequency, nocturia, and nocturnal enuresis,involuntary leakage of urine, voiding frequency >8 per 24 hours, voidingdysfunction such as hesitancy, straining, poor stream, and incompleteemptying.

IV. Vaginal Conditions

The intravaginal device of the invention may be configured to administerenergy from one or more energy transmitters, which may be used intherapeutic applications to treat a pelvic floor or vaginal disorder.Exemplary vaginal disorders are vaginal laxity, pelvic organ prolapse,incontinence, tissue tone (e.g., moisture and tightness), nervesensitivity, orgasmic dysfunction, vulvovaginal laxity (e.g., in labialand vaginal tissues), atrophic vaginitis, stress incontinence, andpubocervical fascia tightening. The energy transmitters may be, forexample, radio frequency transmitters, lasers, or electricalstimulators. RF transmitters provide nonablative radio frequency in theform of thermal energy to treat vaginal and pelvic floor disorders byheating tissue. By applying heat to the affected tissue, the thermaldamage stimulates collagen production in deep layers of the skin andsubcutaneous tissue to strengthen and fortify the collagen network inthe vagina and surrounding area. This strengthens the tissues in areascritical for maintaining pelvic floor and vaginal health.

V. Drug Delivery

An intravaginal device of the invention may be configured to administer,e.g., locally or systemically, a pharmaceutical agent (e.g., acomposition comprising a pharmaceutical agent) useful in the treatmentof a pelvic floor disorder (PFD) such as, but not limited to, urinaryincontinence (UI), stress urinary incontinence (SUI), urge incontinence,mixed stress and urge urinary incontinence, dysuria (e.g., painfulurination), anal or fecal incontinence, pelvic organ prolapse (POP)(e.g., urethra prolapse (urethrocele), bladder prolapse (cystocele), orboth urethra and bladder prolapse (cystourethrocele), vaginal vault andcervix prolapse (vaginal vault prolapse), uterus prolapse (uterineprolapse), rectum prolapse (rectocele), sigmoid colon prolapse(sigmoidocele), and small bowel prolapse (enterocele)), pelvic pain,sexual dysfunction (e.g., coital incontinence, a sexual pain disorder,dyspareunia, vaginismus, and/or impaired sexual arousal), weak orimpaired pelvic floor muscle function, post-labor issues or damage, painand/or incontinence caused by damage to a lumbosacral nerve, nonrelaxingpelvic floor dysfunction, and/or the symptoms thereof (e.g., changes tomuscle tone, changes to muscle strength, bladder leakage, anal or fecalleakage, pain, frequency, and urgency), or another disease or conditionaffecting a female subject, e.g., as described herein).

Delivery of a pharmaceutical agent to the tissues of the vagina may becoordinated with the performance of a pelvic floor training exercise(e.g., a PFL or PFR), such that the pharmaceutical agent is deliveredprior to, during, or after use of the intravaginal device to perform apelvic floor exercise (e.g., a PFL or PFR). In some instances,administration of a pharmaceutical agent may be delivered by anintravaginal device of the invention that is configured to provide dailymonitoring (e.g., in substantially real-time) in response to ameasurement while a user performs her daily activities. Selection of apharmaceutical agent to be incorporated into an intravaginal device ofthe invention may be made by, e.g., a medical practitioner, e.g.,overseeing the treatment of an individual having a PFD or by the deviceuser. The pharmaceutical agent may be one that is used to treat orameliorate a PFD, or a symptom thereof. Alternatively, or in additionto, the intravaginal device may be configured to deliver apharmaceutical agent suitable for the treatment a condition and/ordisease of the vaginal tissues and/or female organs that, e.g., althoughunrelated to pelvic floor dysfunction, may be present in patients, suchas those having a PFD. Non-limiting examples of such diseases and/orconditions include sexually transmitted diseases (STDs), yeastinfections (e.g., candida vulvovaginitis), bacterial infections (e.g.,bacterial vaginosis), parasitic infections (e.g., trichomoniasis),infection of the cervix (e.g., cervicitis), cancer (e.g., vaginal,vulva, cervical, ovarian, endometrial, and/or breast cancer), vaginitis(e.g., infectious and/or noninfectious vaginitis), endometriosis,vaginal pain, vulvar pain (e.g., vulvodynia), vulvar or vaginal injury,pudendal neuralgia, and vaginal skin conditions (e.g., vaginaldermatitis).

To treat a PFD and/or a condition of the vaginal tissue and femaleorgans, or a symptom thereof, the intravaginal device may be insertedinto the vaginal cavity and the pharmaceutical agent (e.g., acomposition comprising a pharmaceutical agent) may be released andabsorbed by the surrounding vaginal tissue, e.g., transdermally and/ortransmucosally. In some instances, the pharmaceutical agent may be,e.g., uniformly dispersed or dissolved throughout the material of theintravaginal device (e.g., the material of the main body and/or tether).In some instances, the pharmaceutical agent may be confined to adelivery module or component (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 ormore delivery modules or components), such as an inner core or reservoirarranged within the main body and/or tether of the intravaginal device.Non-limiting examples of delivery modules that may be incorporated intoan intravaginal device of the invention are described in, e.g., Malcolmet al. (Int. J. Women. Health. 4:595-605, 2012); U.S. Publication Nos.US20090004246A1 and US20070043332A1; U.S. Pat. Nos. 6,394,094,5,972,372, 8,333,983, 6,436,428, and 6,126,958, 3,991,760, 4,215,691,and 4,402,695; and International Publication Nos. WO200170154 andWO2012065073A2, each of which are herein incorporated by reference intheir entirety. A pharmaceutical agent may also be applied to thesurface of the intravaginal device (e.g., the main body and/or tether)as a coating, layer, or gel.

A pharmaceutical agent may be released from an intravaginal device ofthe invention, e.g., at a rate that does not change with time(zero-order release). During zero-order release a therapeuticallyeffective dose is maintained by the delivery system, e.g., theintravaginal device comprising a delivery module. For example, sustainedpharmaceutical agent delivery may be obtained with an intravaginaldevice of the invention that has been configured to contain a reservoirsystem, which consists of, e.g., tubes, fibers, laminates, ormicrospheres. In these systems, a reservoir may be coated in arate-controlling membrane. Pharmaceutical agent diffusion across themembrane is rate limiting and is constant (zero order) as long as themembrane's permeability does not change and as long as the concentrationof pharmaceutical agent in the reservoir is constant.

In another example, when a pharmaceutical agent is dispersed through amaterial (e.g., a polymeric material, e.g., a monolithic system) of theintravaginal device (e.g., the main body and/or tether), thepharmaceutical agent may be released as it diffuses through thematerial. In this example, the pharmaceutical agent is released from theouter surface of the material first. As this outer layer becomesdepleted the pharmaceutical agent is released from further within thematerial. Because the pharmaceutical agent must also diffuse through thedepleted material, the net result is that the release rate slows downproducing a delayed release effect.

The configuration of the intravaginal device can be selected, e.g., by amedical practitioner, to suit the therapeutic needs of the individualpatient, e.g., a patient having a PFD and suitable for treatment with anintravaginal device of the invention. Additionally, a plurality ofdesign configurations may be combined so as to allow more than onepharmaceutical agent (e.g., 1, 2, 3, 4, 5, or more pharmaceuticalagents) to be released according to established guidelines, e.g., atdosage amounts authorized by the FDA or other regulatory agency. Anintravaginal device of the invention may contain a combination of adelivery module or component and a core of material containing apharmaceutical agent for sustained or directed release. For example, theintravaginal device may be composed of a material in which apharmaceutical agent is dispersed and also include at least oneadditional inner core or reservoir (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,or more additional inner cores or reservoirs) containing thepharmaceutical agent(s).

Use of an intravaginal device of the invention to administer apharmaceutical agent may allow for nondaily, low dose, and continuousdosing with a pharmaceutical agent, which may result in, e.g., stabledrug levels, a lower incidence of side effects, and/or improved patientcompliance with a treatment regime, e.g., one provided by a medicalpractitioner, including administration of the pharmaceutical agentand/or a pelvic floor training exercise (e.g., a PFL or PFR).

Non-limiting examples of pharmaceutical agents, or combinations thereof,that can be administered using an intravaginal device of the inventionare described below and may include those described, e.g., in, e.g.,Drutz et al. (“Female Pelvic Medicine and Reconstructive PelvicSurgery.” Springer, London. 2003), Hussain et al. (J. of ControlledRelease. 103:301-313, 2005), Santoro et al. (“Pelvic Floor Disorders:Imaging and Multidisciplinary Approach to Management.” Springer, London.2010), and U.S. Publication No. US20110045076A1, each of which areherein incorporated by reference in their entirety.

Anticholinergic (Antimuscarinic) Agents

Anticholinergic agents block the neurotransmitter acetylcholine in thecentral and the peripheral nervous system and may depress both voluntaryand involuntary bladder contractions, thereby, e.g., suppressinginvoluntary bladder contraction. Anticholinergic agents are commonlyused in the treatment of, e.g., urge urinary incontinence (UUI),overactive bladder syndrome (OAB), and nocturnal enuresis. In addition,they may increase the urine volume at which first involuntary bladdercontraction occurs, decrease the amplitude of the involuntary bladdercontraction, and increase bladder capacity. Non-limiting examples ofanticholinergic agents that may be delivered to a subject in need oftreatment for, e.g., involuntary bladder contraction using anintravaginal device of the invention include, e.g., atropine (e.g.,ATROPEN®), scopolamine (e.g., TRANSDERM SCOP®), dicyclominehydrochloride (e.g., BENTYL®), darifenacin (e.g., ENABLEX®), solifenacinsuccinate (e.g., VESICARE®), hyoscyamine sulfate (e.g., LEVSIN® andCYSTOSPAZ-M®), propantheline (e.g., PRO-BANTHINE®), tolterodine (e.g.,DETROL® and DETROL LA®), propiverine (e.g., DETRUNORM®), trospium (e.g.,SANCTURA®), fesoterodine (e.g., TOVIAZ®), bethanechol (e.g.,URECHOLINE®), and carbachol (e.g., MIOSTAT® and CARBASTAT®).

Anticholinesterase Inhibitors

Acetylcholinesterase inhibitors inhibit the acetylcholinesterase enzymefrom breaking down acetylcholine, thereby increasing both the level andduration of action of the neurotransmitter acetylcholine.Acetylcholinesterase inhibitors have been used to treat, e.g., overflowincontinence. A non-limiting example of an acetylcholinesteraseinhibitor that may be delivered to a subject in need of treatment for,e.g., overflow incontinence using an intravaginal device of theinvention is distigmine.

Alpha-adrenergic Agonists

Alpha-adrenergic agonists (e.g., α1 and α2 agonists) selectivelystimulate alpha-adrenergic receptors (e.g., α1 and α2 receptors) and maybe useful, e.g., in increasing bladder outlet resistance by contractingthe bladder neck, and may be delivered to a subject in the treatment of,e.g., mild to moderately severe stress urinary incontinence (SUI) usingan intravaginal device of the invention. Non-limiting examples ofalpha-adrenergic agonists that may be delivered with an intravaginaldevice of the invention include, e.g., midodrine (e.g., AMATINE®,PROAMATINE®, and GUTRON®), pseudoephedrine hydrochloride (e.g.,SUDAFED®), phenylpropanolamine, ephedrine, and norephedrine.

Alpha-Adrenergic Antagonists

Alpha-adrenergic antagonists (e.g., alpha-blockers, such as α1- andα2-blockers) act as neutral antagonists or inverse agonists ofalpha-adrenergic receptors (e.g., α1 and α2 receptors) and have beenused, e.g., to treat UUI and OAB. They have shown some success, e.g., inpatients who have decentralized or autonomous bladders as the result ofmyelodysplasia, spinal cord injury, or radical pelvic surgery.Non-limiting examples of alpha-adrenergic antagonists that may bedelivered with an intravaginal device of the invention to a subject inneed of treatment for, e.g., UUI and/or OAB, include phenoxybenzamine(e.g., DIBENZYLINE®), prazosin (e.g., MINIPRESS®), alfuzosin (e.g.,UROXATRAL®), doxazosin (e.g., CARDURA®), terazosin (e.g., HYTRIN®), andtamsulosin (e.g., FLOMAX®).

Beta-Adrenergic Agonists

Beta-adrenergic agonists act upon the beta adrenoceptors (e.g., β1- andβ2-receptors), e.g., to increase intraurethral pressure and to treatSUI, UUI, and OAB. Non-limiting examples of beta-adrenoceptor agoniststhat may be delivered with an intravaginal device of the invention to asubject in need of treatment for, e.g., SUI, UUI, and/or OAB, includeterbutaline (e.g., BRETHINE®, BRICANYL®, and BRETHAIRE®), clenbuterol(e.g., SPIROPENT® and VENTIPULMIN®), and salbutamol (e.g., VENTOLIN®)

Antispasmodic Agents

Antispasmodic agents, e.g., relax the smooth muscles of the urinarybladder. By exerting a direct spasmolytic action on the smooth muscle ofthe bladder, these medications have been reported to, e.g., increasebladder capacity and effectively decrease or eliminate urgeincontinence. Non-limiting examples of antispasmodic agents that may bedelivered with an intravaginal device of the invention to a subject inneed of treatment for, e.g, to increase bladder capacity and/or todecrease or eliminate urge incontinence, include, e.g., calciumantagonists, potassium channel openers, oxybutynin chloride (e.g.,DITROPAN® IR, DITROPAN XL®, and GELNIQUE®), flavoxate (e.g., URISPAS®),emepronium bromide (e.g., CETIPRIN®), imidafenacin (e.g., URITOS®),meladrazine, mirabegron (e.g., MYRBETRIQ®), and terodiline.

Antidepressants

Tricyclic antidepressants (TCAs) have been traditionally used to treatmajor depression, however, TCAs have an additional use in the treatmentof bladder dysfunction, e.g., SUI. TCAs function to increasenorepinephrine and serotonin levels and may exhibit, e.g., ananticholinergic and direct muscle relaxant effect on the bladder.Non-limiting examples of TCAs that may be delivered with an intravaginaldevice of the invention to a subject in need of treatment for, e.g, SUI,include, e.g., imipramine hydrochloride (e.g., TOFRANIL®) andamitriptyline hydrochloride (e.g., ELAVIL®). Other antidepressants, suchas serotonin/norepinephrine reuptake inhibitors may also improve, e.g.,stress incontinence. Non-limiting examples of serotonin/norepinephrinereuptake inhibitors that may be delivered with an intravaginal device ofthe invention to a subject in need of treatment for, e.g, stressincontinence, include, e.g., duloxetine (e.g., CYMBALTA®).

Hormones

Hormones such as estrogens, progestogens, testosterone, post-menopausalhormones, and derivatives thereof may be delivered with an intravaginaldevice of the invention. Treatment with hormones may serve, e.g., tonourish and strengthen the tissues of the pelvic floor. For example,estrogens may be able to increase urethral closure pressure, improve thetransmission of abdominal pressure to the proximal urethra, and increasethe sensitivity threshold of the bladder. Estrogens have been used,e.g., to treat SUI, in combination with other drugs, such asalpha-adrenergic agonists.

Non-limiting examples of estrogens that may be delivered with anintravaginal device of the invention to a subject in need of treatmentfor, e.g, SUI and/or to increase urethral closure pressure, improve thetransmission of abdominal pressure to the proximal urethra, and/or toincrease the sensitivity threshold of the bladder include, e.g.,conjugated estrogen (e.g., PREMARIN®), estradiol, estrone, estriol,17α-estradiol, 4-hydroxyestradiol, 2-hydroxyestradiol, estrone3-sulfate, moxestrol, diethylstilbestrol, hexestrol, dienestrol,tamoxifen, 4-hydroxytamoxifen, clomifene, nafoxidine, ICI-164384,5-androstenediol, 4-androstenediol, 3β-androstanediol,3α-androstanediol, dehydroepiandrosterone, 4-androstenedione,coumestrol, genistein, β-zearalanol, and bisphenol A.

Non-limiting examples of progestogens that may be delivered with anintravaginal device of the invention to a subject in need of treatmentfor, e.g, SUI and/or to increase urethral closure pressure, improve thetransmission of abdominal pressure to the proximal urethra, and/or toincrease the sensitivity threshold of the bladder include, e.g.,progesterone, dydrogesterone, chlormadinone acetate, cyproteroneacetate, megestrol acetate, medroxyprogesterone, medrogestone,demegestone, nomegestrol acetate, promegestone, trimegestone,segesterone acetate, norethisterone, norethisterone acetate,lynestrenol, noretynodrel, levonorgestrel, norgestimate, desogestrel,etonogestrel, gestodene, dienogest, tibolone, and drospirenone.

Prostaglandin Synthesis Inhibitors

Prostaglandin synthesis inhibitors are agents that prevent theproduction of prostaglandins, which may cause contraction of thebladder, e.g., by inhibition of the cyclooxygenase (COX) enzymes.Prostaglandin synthesis inhibitors have been used, e.g., to treat UUIand OAB. Non-limiting examples of prostaglandin synthesis inhibitorsthat may be delivered with an intravaginal device of the invention to asubject in need of treatment for, e.g, UUI and/or OAB, include, e.g.,nonsteroidal anti-inflammatory agents (NSAIDs) (e.g., salicylates,propionic acid derivatives, acetic acid derivatives, enolic acidderivatives, anthranilic acid derivatives, selective COX-2 inhibitors,and sulfonanailides) and steroidal anti-inflammatory agents. Forexample, the NSAID may be selected from indomethacin (e.g., INDOCIN® andTIVORBEX®), flurbiprofen (e.g., OCUFEN®), aspirin, celecoxib(CELEBREX®), diclofenac (CATAFLAM®, ZIPSOR®, ZORVOLEX®), diflunisal,etodolac, ibuprofen (MOTRIN®, ADVIL®), indomethacin (INDOCIN®),ketoprofen, ketorolac, nabumetone, naproxen (ALEVE®), oxaprozin(DAYPRO®), piroxicam (FELDENE®), salsalate, sulindac, and tolmetin

Vasopressin Analogues

Vasopressin analogues are similar in function but not necessarilysimilar in structure to vasopressin (ADH) and have been used, e.g., toreduce detrusor over-activity in the treatment of OAB. A non-limitingexample of a vasopressin analogue that may be delivered with anintravaginal device of the invention to a subject in need of treatmentfor, e.g., OAB, includes, e.g., desmopressin (e.g., DDAVP®).

Botulinum Toxins

Botulinum toxin is a neurotoxic protein produced by the bacteriumClostridium botulinum and is used to treat a number of disorderscharacterized by overactive muscle movement, e.g., OAB. For example,injections with botulinum toxin have been shown to decrease episodes ofurinary leakage, reduce bladder voiding pressures, and post-voidresidual urgency. Non-limiting examples of botulinum toxins that may bedelivered with an intravaginal device of the invention to a subject inneed of treatment for, e.g, OAB, include, e.g., botulinum toxin A (e.g.,BOTOX®) and botulinum toxin B (e.g., MYOBLOC®).

Muscle Relaxants

Non-limiting examples of muscle relaxants that may be used to treat apatient with, e.g., pelvic floor pain, high pelvic floor muscle toneand/or muscles spasms, may be delivered with an intravaginal device ofthe invention include, e.g., baclofen (e.g., LIORESAL®), chlorzoxazone(e.g., LORZONE®), carisoprodol (e.g., Soma®), cyclobenzaprine (e.g.AMRIX®), dantrolene (e.g., DANTRIUM® and RYANODEX®), diazepam (e.g.,VALIUM®), metaxalone (e.g., SKELAXIN®), methocarbamol (e.g. ROBAXIN®),and tizanidine (e.g., ZANAFLEX®).

Agents that Stimulate Muscles and/or Prevent Muscle Mass Loss

Non-limiting examples of agents that stimulate muscles and/or preventmuscle mass loss that may be delivered, e.g., to aging patients, totreat, e.g., a PFD including muscle atrophy, with an intravaginal deviceof the invention include, e.g., β-hydroxy β-methylbutyrate (HMB), aminoacids (e.g., such as lysine and the branched chain amino acids (BCAAs)leucine, isoleucine, and valine), anabolic steroids (e.g.,methandrostenolone), and selective androgen receptor modulators (SARMs).

Other Pharmaceutical Agents

In addition to delivering pharmaceutical agents useful in the treatmentof a PFD, or a symptom thereof, an intravaginal device of the inventionmay be configured to deliver a pharmaceutical agent useful in thetreatment of an additional disease or condition that may be present inan individual having a PFD. In some instances, an individual identifiedas having a PFD suitable for treatment with an intravaginal device ofthe invention may already be using a vaginal device (e.g., acontraceptive or hormone replacement device), pessary, or suppository toadminister a pharmaceutical agent to treat an additional disease orcondition. In some instances, the additional disease or condition isidentified after the individual has begun treatment for a PFD with anintravaginal device of the invention. To improve patient compliance withtreatment for a PFD using an intravaginal device of the invention, theintravaginal device may be configured to deliver a pharmaceutical agentused to treat the additional disease or condition, e.g., to reduce theoccurrence of the intravaginal device being removed during treatment forthe secondary disease or condition and not reinserted. Additionally, anintravaginal device of the invention may be configured to deliver apharmaceutical agent, e.g., a contraceptive agent, to substitute acontraceptive device that could not be worn during treatment for a PFDwith an intravaginal device of the invention.

Non-limiting examples of other agents that may be delivered with anintravaginal device of the invention to treat an additional disease orcondition, e.g., such as those described herein, include, e.g.,microbicides (e.g., to reduce the infectivity of microbes, such asviruses or bacteria); hormone replacement and/or contraceptive agents(e.g., a estrogenic compound, a progestational compound, and/or agonadotropin releasing hormone); estrogen receptor modulators (e.g., totreat vaginal atrophy and/or dyspareunia), antiviral agents (e.g., totreat sexually transmitted diseases, such as HIV), antibacterial agents(e.g., to treat bacterial vaginosis), anticancer agents (e.g., to treatendometrial, ovarian, cervical, vulvar, vaginal, or fallopian tubecancer), therapeutic peptides and proteins (e.g., to treat vaginalinfections), benzodiazepines (e.g., to treat interstitial cystitis(IC)), and analgesics (e.g., to treat pain associated with a PFD and/ora cancer).

VI. Devices of the Invention

A device of the invention that can be used to diagnose, monitor, ortreat a pelvic floor disorder (PFD) or vaginal disorder is depicted inFIGS. 1-2. FIG. 1 depicts intravaginal device 100 with main body 110 andtether 10. The device may also be used to detect a predetermined eventor collect data related to various physiological indicia collected fromsensors on the device. Tether 10 may contain, for example, 1-20 sensors200 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20 or more sensors 200). Main body 110 may also contain, forexample, 1-20 sensors 200 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20 or more sensors) and 1-20 (e.g., 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more)energy transmitters 210 (e.g., RF, laser, electrical stimulation).Tether 10 or main body 110 may be flat or oblong. The sensors in tether10 may be MEMS sensors. Tether 10 may also contain a Bluetooth chipand/or an Apple chip or other wireless compatible chipset. Main body 110may be configured to administer at least one (e.g., 1, 2, 3, 4, 5, ormore) pharmaceutical agent to the vaginal tissues for the treatment of aPFD, a vaginal disorder, or the symptoms thereof, or other disease orcondition. In some instances, tether 10 may be similarly configured toadminister a pharmaceutical agent to the vaginal tissues. Configuringtether 10, which may be detachable from main body 110, forpharmaceutical administration would provide the user the option of beingable to replace and/or exchange the tether as needed, e.g., when thepharmaceutical agent has been depleted, when a different pharmaceuticalagent is required, or when a different dosage is required, without theneed to discard main body 110. Tether 10 may have gradations or rulermarkings to visualize how deep intravaginal device 100 is within thevagina. In any of the embodiments described herein, the tether may beoptionally absent.

Intravaginal device 100 contains at least one sensor 200 within tether10 for monitoring pelvic floor muscle movement. As depicted in FIG. 1,intravaginal device 100 contains circuit board 700 within main body 110.Circuit board 700 can be a flexible circuit board that connects multiplecomponents of intravaginal device 100 to each other, such as sensor 200,battery 800, microcontroller 900, transmitter/receiver 1000, datastorage unit 1100, sensory output component 1200, wireless communicationantennae 1300, ON/OFF switch 1600, and authentication chip 1400 (FIG. 1,inset). Circuit board 700 can alternatively be connected to sensor 200by a wire. Circuit board 700 and all its connected components mayalternatively be positioned in tether 10. Intravaginal device 100 may beconfigured with additional sensors and/or delivery modules.

Intravaginal device 100 can be inserted into a subject and deployed at aposition in proximity to the cervix, vaginal fornix, or vaginal cuff,substantially parallel to the surface of the upper vagina adjacent tothe pelvic floor, manually or by using insertion tool 600. Intravaginaldevice 100 may also contain molded wing 300 for stabilizing the deviceat a position in proximity to the cervix or vaginal cuff of a patient(FIG. 1). Tether 10 may also be in the form of a detachable cable thatcan be used to connect intravaginal device 100 to transmitter/receiverbox 500 and to assist in the removal of intravaginal device 100 from apatient.

Transmitter/receiver box 500 and/or transmitter/receiver 1000 connectswirelessly to electronic device 1500, via a Wi-Fi and/or Bluetoothconnection

In certain embodiments, intravaginal device 10 contains 8 or fewer(e.g., 4 or 5) sensors 200 in tether 10 and 5 or fewer sensors 200 inmain body 110. One sensor may be shared by both the tether and main body(FIG. 2). The angle between the plane connecting the anterior andposterior aspects of the main body 110 and tether 10 may vary from0°-180° (e.g., 10°, 20°, 30°, 40°, 50°, 60°, 70°, 80°, 90°, 100°, 110°,120°, 130°, 140°, 150°, 160°, 170°, 180°. The circumference of main body110 may be from about 10 cm to about 50 cm (e.g., 15 cm, 20 cm, 25 cm,30 cm, 35 cm, 40 cm, 45 cm, or 50 cm) or may be 27.6 cm. The length oftether 10 may be from about 3 cm to about 50 cm (e.g., 5 cm, 10 cm, 15cm, 20 cm, 25 cm, 30 cm, 35 cm, 40 cm, 45 cm) or may be 25.5 cm long.The sensors 200 may be spaced about 0.5 cm to about 5 cm (e.g., 1 cm,1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm) or may be spaced about1.6 cm apart. At least one sensor 200 may be placed on tether 10 cm orless (e.g., 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, or 1 cm)from main body 110.

The tether may be configured as a separable tether with one or morecomponents. Having a separable tether allows the device to have along-term wearable portion (e.g., ring 110 and part of tether 10; e.g.,long-term wearable device 105) and a short-term wearable portion (e.g.,short-term wearable portion 115) that can connect to a power supply forpowering or recharging a local battery. This can be used for powering anintravaginal device with an RF transmitter(s) for therapeuticapplications. RF transmitters may require power in the range of 10 mW to300 W. Thus, in the event that a wireless power source (e.g., a battery)cannot sustain this power for an extended duration, the separableportion(s) of the tether can be configured for connection to a powersource (e.g., an AC power source) to recharge the device or directlypower the RF transmitter(s). The separable tether allows flexibility andmodularity by permitting the intravaginal device to be used in eithershort-term (e.g., 1-30 minutes) or long term (e.g., 30 minutes orlonger, e.g., 1 day-6 months) capacities.

If configured to be separation, the portions of the tether may furtherinclude connections, such as magnetic or interlocking connections (e.g.,press fit, snap fit) that can be used to join the portion(s). Theconnections may also be configured to be electrical connections that canbe used to supply power to the intravaginal device.

Also featured is a peripheral device that may be configured with aprocessing unit that can transform or utilize sensor data received fromthe intravaginal device when a user performs a daily activity (e.g.,activity that alters (e.g., increases and/or decreases) the overallhealth of her urogenital system and/or pelvic floor) to provide feedbackto the user regarding whether the detected activity affects her healthstatus. The peripheral device can process the sensor data to produce abaseline that can be used for comparison to sensor data obtained at afuture time to provide feedback to the user (e.g., an alert) regardingwhether activities she performs are beneficial or detrimental to herhealth status. The peripheral device can process the sensor data andcompare the result to a previously established or predetermined baselineand based on the comparison can provide feedback to the user (e.g., analert) regarding whether activities she performs are beneficial ordetrimental to her health status. The peripheral device is configuredfor communication with the intravaginal device and the sensors in theintravaginal device.

VII. Additional Device(s) that May be Used in Conjunction with anIntravaginal Device of the Invention

An intravaginal device of the invention may be used (e.g.,simultaneously and/or consecutively) with an additional device that isconfigured to treat a PFD and/or another disease or condition.Non-limiting examples of additional devices that may be used incombination with an intravaginal device of the invention include, butare not limited to, a vaginal pessary, a vaginal and/or analsuppository, a catheter (e.g., a urethral and/or rectal catheter, suchas a device described in U.S. Publication No. US20150112231A1 and inInternational Publication Nos. WO2011050252A1 and WO2013082006A, each ofwhich is herein incorporated by reference in their entirety), a bladderneck support device, a vaginal sponge, a menstrual device (e.g., atampon or a menstrual cup), a vaginal stimulator (e.g., a device thatcontains one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 electrodes;a device that contains a vibrator; and/or a device that contains a lightemitting source), a vaginal dilator, a vaginal specula, a urine seal, aurethral insert, an artificial urinary and/or anal sphincter, and/or adevice that contains a camera.

VIII. Kits

Also featured are kits containing an intravaginal device for use in theprevention and treatment of pelvic floor disorders (PFDs). Such kits canbe used to treat an individual (e.g., a female patient) who may benefitfrom pelvic floor muscle training (PFMT) that includes the performanceof pelvic floor lifts (PFLs) and/or pelvic floor relaxations (PFRs). Insome instances, the kit may include an intravaginal device of theinvention that is configured to monitor the overall health status of auser's urogenital system and/or pelvic floor (e.g., the muscle fibers ofthe levator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues). A kit fortreating or reducing the progression of a pelvic floor disorder in anindividual may include an intravaginal device of the invention and oneor more of a transmitter and receiver, a detachable cable, a tool forinsertion of the intravaginal device, an electronic device, a database,and/or a user interface, a power source (e.g., one or more batteries),and instruction for use thereof. The kit may also include a variety ofseparable tether portions or modules and/or sleeves, e.g., one or moretether modules or separable tether portions and/or sleeves that each mayinclude a sensor and/or a delivery module, as described herein, that maybe used to expand the functionality of the intravaginal device.Additionally, the kit may contain an additional device, as describedherein, a charger, a sanitary cleaner, and/or gloves.

Other optional components of the kit include a lubricant (e.g., alubricant compatible with the material from which the intravaginaldevice is fabricated, e.g., silicone) for use in inserting theintravaginal device and/or a biomaterial (e.g., hyaluronic acid) for usein improving the adhesion of the intravaginal device at a positionproximal to the cervix or vaginal cuff of an individual. The optionalcomponents (e.g., the lubricant and/or biomaterial) may be provided in aseparate container (e.g., a sealed packet, tube, and/or applicator).

Additionally, a pharmaceutical agent useful in treating a PFD, or thesymptoms thereof, or other disease or condition, as described herein,may also be supplied with a kit of the invention. The pharmaceuticalagent may be supplied in any format (e.g., within a tube, vial, orpre-filled syringe) and with the necessary accessories (e.g., a needle,syringe, dropper, and/or brush) required to, e.g., fill or refill adelivery module or, e.g., to apply a coating, layer, or gel to theintravaginal device.

Alternatively, the optional components (e.g., the lubricant and/orbiomaterial) can be provided pre-applied to the intravaginal device,such that the intravaginal device is ready for insertion and use.Additional optional components of the kit include sterile gloves (e.g.,at least one pair) for use in the insertion and/or removal of theintravaginal device, or alternatively for use during the application ofthe lubricant and/or biomaterial to the intravaginal device, and/or astorage container for the intravaginal device and/or the system of theinvention.

A kit of the invention may be useful in the treatment of a pelvic floordisorder such as, but not limited to, urinary incontinence (UI), stressurinary incontinence (SUI), urge incontinence, mixed stress and urgeurinary incontinence, dysuria (e.g., painful urination), anal or fecalincontinence, pelvic organ prolapse (POP) (e.g., urethra prolapse(urethrocele), bladder prolapse (cystocele), or both urethra and bladderprolapse (cystourethrocele), vaginal vault and cervix prolapse (vaginalvault prolapse), uterus prolapse (uterine prolapse), rectum prolapse(rectocele), sigmoid colon prolapse (sigmoidocele), and small bowelprolapse (enterocele)), pelvic pain, sexual dysfunction (e.g., coitalincontinence, a sexual pain disorder, dyspareunia, vaginismus, and/orimpaired sexual arousal), weak or impaired pelvic floor muscle function,post-labor issues or damage, pain and/or incontinence caused by damageto a lumbosacral nerve, and nonrelaxing pelvic floor dysfunction.

IX. Methods of Use

Methods of Treating or Monitoring the Health State of a Pelvic Floor orVaginal Disorder

Discussed below are methods of treating or monitoring the health stateof a subject (e.g., the state of a pelvic floor or vaginal disorder) byusing an intravaginal device and/or a peripheral device, as discussedherein. The intravaginal device may be configured for use with orwithout the peripheral device. The intravaginal device may have one ormore sensors configured to collect various physiological data of thesubject (e.g., pelvic floor movement data). These data can then beprocessed by the peripheral device using one or more computationalalgorithms that transform the data and/or present the data in a usefulmedium (e.g., on a graphical user interface) for a user or a health careprofessional.

A female patient perform pelvic floor lifts (PFLs) and/or pelvic floorrelaxations (PFRs) in order to treat, inhibit, or reduce the developmentof or progression of a pelvic floor disorder (PFD) or one or more othervaginal disorders, as described herein. The PFLs and PFRs can bemonitored using the one or more sensors of the intravaginal device.Initially, the intravaginal device can be inserted into the vagina ofthe individual and the engagement of or relaxation of a pelvic floor(PF) muscle (e.g., the levator ani (e.g., the pubococcygeus,ileococcygeus, coccygeus, and puborectalis muscles) and the associatedconnective tissues which spans a spheric form from the pubic boneanteriorly to the sacrum posteriorly and to the adjoining bony structurejoining these two bones) of the individual can be monitored with theintravaginal device. Treatment with the device reduces the frequency ofoccurrence and/or severity of at least one (e.g., 1, 2, 3, 4, 5, 6, 7,8, 9, 10, or more) symptom of a pelvic floor disorder. In particular,treatment includes activating of the pelvic floor muscles and measuringthe performance of a pelvic floor lift (PFL), which is an exercisecharacterized by an upward movement (e.g., a lifting movement, e.g., amovement in the cranial direction) of the pelvic floor and/or measuringthe performance of a pelvic floor relaxations (PFR) (e.g., a downwardmovement, e.g., a movement in the caudal direction) of the pelvic floorusing the device. In some instances, treatment includes using anintravaginal device of the invention that is configured to monitor(e.g., in substantially real-time) the overall health status of a user'surogenital system and/or pelvic floor (e.g., the muscle fibers of thelevator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues). The device canbe used to measure at least one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)or more performance metrics and/or at least one (e.g., 1, 2, 3, 4, 5, 6,7, 8, 9, or 10) or more characteristic of an individual's pelvic floordisorder (PFD) including, but are not limited to, pressure (e.g., musclecontraction), temperature, pH, and muscle quality. The device can alsobe used to deliver therapeutic energy (e.g., with an RF transmitter) topromote healing of damaged vaginal tissue.

A patient can use the intravaginal device of the invention to treat avaginal disorder or PFD over a treatment period ranging from about oneweek to about three months (e.g., about 1-week, 2-weeks, 3-weeks,4-weeks, 2-months, or 3-months, e.g., about 7-21 days, 7-35 days, 7-49days, 7-63 days, 7-77 days, 7-91 days, or 7-105 days, e.g., about 2-8weeks). The intravaginal device can remain inside the patient during thetreatment period to monitor the patient's pelvic floor muscles (e.g.,muscle quality, muscle tone, pH) and the performance of PFLs and/orPFRs. The patient can also remove the device during the treatment periodand can reinsert the device after disinfection (e.g., washing) toreinitiate treatment. The intravaginal device can monitor and collectdata from its sensor(s) (e.g., at least one sensor, e.g., 1, 2, 3, 4, 5,6, 7, 8, 9, 10, or more sensors) substantially continuously orperiodically. The sensors can measure at least one (e.g., 1, 2, 3, 4, 5,6, 7, 8, 9, or 10) or more performance metrics (e.g., the quality and/orquantity of PFLs and/or PFRs performed) and/or at least one (e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, or 10) or more characteristic of an individual'sPFD (e.g., muscle quality and muscle tone). In some instances, themonitoring (e.g., monitoring of pelvic floor movement, of a performancemetric, and/or characteristic of an individual's PFD) can occur afterthe intravaginal device has received a signal (e.g., a command) from theindividual using the intravaginal device to begin collecting data. Thissignal may be a signal from a button (e.g., a button within a softwareapplication running on an electronic device wirelessly connected to theintravaginal device) which is pressed by the individual prior toperforming a series of PFLs and/or PFRs with the intravaginal device.

The treatment program can include performing a series of one (e.g., 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, or 70) or moretherapeutic energy treatment regimens, PFLs and/or PFRs (e.g., engagingthe pelvic floor muscles to achieve a lift and/or a relaxation) with theintravaginal device. The therapeutic energy treatment regimens, PFLsand/or PFRs can be performed over a set time interval (e.g., 1-5minutes, 1-60 seconds, or 15 seconds) with the intravaginal device. Forexample, a series can be divided into a period of time (e.g., about 1second-30 seconds, such as 1 second, 15 seconds, or 30 seconds, or up to1 minute, or more) during which the therapeutic energy treatmentregimens, PFLs and/or PFRs are performed and a period of rest (e.g.,about 1 second-30 seconds, such as 1 second, 15 seconds, or 30 seconds,or up to 1 minute, or more) where no PFL and/or PFR are performed. Insome instances, each series (e.g., a series including a set number ofPFLs and/or PFRs performed, or a series of PFLs and/or PFRs performedover a set time interval) occurs in about 1 second to about 10 minutes(e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, or 60 seconds,e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 minutes). In some instances, theseries includes performing PFLs and/or PFRs with the device for 15seconds and then resting for 15 seconds. A patient may repeat a seriesat least one additional time (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10times) during a treatment period. An exemplary method of treatment withan intravaginal device of the invention includes a patient performing aseries PFLs and/or PFRs for 15 seconds and then resting for 15 seconds,and repeating the series five times over about a 90-second (e.g., 2.5minute) treatment period. Such an exemplary treatment program can beperformed at least once per day (e.g., 1×, 2×, 3×, 4×, or 5× per day).In some instances, the treatment program is determined by, or evaluatedby, a medical practitioner. In other instances, the treatment program isdetermined by the individual. For example, an individual whoself-identifies as having a need to train her pelvic floor muscles basedon her experience of at least one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,or more) symptom of a PFD or vaginal disorder.

During use, the device can provide indicia to the user regarding thequality and tone of the pelvic floor muscles, e.g., as detected by oneor more of the sensors. In particular, the device may include abioimpedence sensor (e.g., an EIM sensor) or a light detecting sensor(e.g., a LiDAR sensor) that can provide information to the user aboutthe quality and tone of the user's pelvic floor muscles before treatmentusing the device, during treatment using the device, and after treatmentusing the device.

During the treatment program the individual may engage with a userinterface on an electronic device that is connected to the intravaginaldevice. The electronic device provides instructions to the user via theuser interface that coach the individual through using the intravaginaldevice of the invention in a treatment program. The instructions may beprovided through a software application running on the electronicdevice. The electronic device generates a readout of results and datathrough the user interface on the quality and quantity of PFLs and/orPFRs performed with the intravaginal device. The readout of results anddata can be observed in substantially real-time or after the completionof the treatment program. The electronic device may instruct theindividual to perform a pelvic floor lift or to relax the pelvic floormuscles, such as through a software application running on theelectronic device. The individual may be instructed to repeat the pelvicfloor lift or to relax the pelvic floor muscles two (e.g., 2, 3, 4, 5,6, 7, 8, 9, 10, 20, 30, 40, or 50) or more times. The electronic devicecollects data on the symptoms experienced by the individual during useof the intravaginal device and provides recommendations for adjustingthe treatment program to improve efficacy. The electronic device canalso notify the individual when to remove the intravaginal device, suchas at the end of the treatment period. A treatment period may concludeafter a pre-determined time (e.g., about one week to about threemonths).

The invention also includes methods of calibrating an intravaginaldevice for treating, or inhibiting or reducing the development orprogression of, a pelvic floor disorder in an individual comprising: (a)inserting the intravaginal device into the vagina of the individual andmonitoring the engagement of, or relaxation of, a pelvic floor muscle ofthe individual with the intravaginal device over a calibration period;and (b) using the data collected over the calibration period tocalculate a baseline score for at least one performance metric of theengagement of, or relaxation of, a pelvic floor muscle of the individualand/or at least one characteristic of the pelvic floor disorder of thesubject. The at least one performance metric of the engagement of, orrelaxation of, a pelvic floor muscle of the individual and/or at leastone characteristic of the pelvic floor disorder is selected from thegroup consisting of the maximum number of pelvic floor lifts and/or themaximum number of pelvic floor relaxations performed, the maximumstrength of a pelvic floor lift and/or a pelvic floor relaxationperformed, and muscle quality muscle strength, and vaginal.

A method of the invention can be used in the treatment of a pelvic floordisorder such as, but not limited to, urinary incontinence (UI), stressurinary incontinence (SUI), urge incontinence, mixed stress and urgeurinary incontinence, dysuria (e.g., painful urination), anal or fecalincontinence, pelvic organ prolapse (POP) (e.g., urethra prolapse(urethrocele), bladder prolapse (cystocele), or both urethra and bladderprolapse (cystourethrocele), vaginal vault and cervix prolapse (vaginalvault prolapse), uterus prolapse (uterine prolapse), rectum prolapse(rectocele), sigmoid colon prolapse (sigmoidocele), and small bowelprolapse (enterocele)), pelvic pain, sexual dysfunction (e.g., coitalincontinence, a sexual pain disorder, dyspareunia, vaginismus, and/orimpaired sexual arousal), weak or impaired pelvic floor muscle function,post-labor issues or damage, pain and/or incontinence caused by damageto a lumbosacral nerve, and nonrelaxing pelvic floor dysfunction.Treatment using a device of the invention may reduce the frequency ofoccurrence and/or severity of at least one symptom of a pelvic floordisorder may be reduced by at least 5% (e.g., 10%, 20%, 30%, 40%, 50%,60%, 70%, 80%, or 90%) or more. In particular, symptoms of pelvic floordisorders that make be ameliorated (e.g., treated, reduced) using amethod of the invention include, but are not limited to, muscle tone(e.g., hypotonic muscle tone and hypertonic muscle tone), poor musclestrength, bladder leakage, anal or fecal leakage, pain (e.g., musclepain, lower back pain, pain during urination, pain during defecation,pain during sexual stimulation and/or intercourse), frequency, andurgency.

A number of MEMS sensors (e.g., 1, 2, 3, 4, 5, 6 or more) may belinearly connected and, e.g., equidistant apart on, e.g., a flex stripencased in a biocompatible material, such as silicone. Each sensor canreflect an angle (location) at a specific point. This angularinformation from the sensors work in conjunction to form a fitted curveor line that reflects the shape and angle of the vagina. The device maybe inserted while sitting or standing.

The device is comfortable, flexible and easy to insert and remove. Thepatient may insert and remove the device herself. Alternatively, ahealth care professional may insert the device (with or without aninsertion tool) and the device may remain inside the patient for up to90 days. The patient can remove the device herself or go to a healthcare professional to have it removed. The device may be flexible, inorder for the device to take the shape of the patient's vagina.

The device may be configured as a multi-use single user device. Thepatient can first download an application to an electronic device, suchas a smartphone, and pair the device with her electronic device. She canthen register the device online and enter her user name and password onthe application to begin using the device. The patient then inserts anduses the device at her convenience. As the vagina is not a sterileenvironment, there is no need to sterilize the device for re-insertion.The patient may regularly wash the probe with mild soap and water beforeand after using the device.

The device may be connected to a transmitter box that wirelessly (e.g.,via Bluetooth) sends the positional data gathered from the vaginaldevice sensors to the electronic device (e.g., a smartphone or computer)that communicates to the patient through an interactive application. Thesensors of the intravaginal device may be used to determine a vaginalangle (θ_(V); FIGS. 3A-3D) of a patient. Baseline measurements ofvaginal angle can be obtained and compared to data obtained after aperiod of performing pelvic floor exercises. For example, for a patientwho is healthy or has mild symptoms of incontinence, the sensors of theintravaginal device may be used to determine a θ_(V) of approximately45° relative to the floor when the patient is standing. When the patientperforms a lift exercise, the sensors of the intravaginal device maydetermine that the θ_(V) increases towards 90°. The exercises may beperformed sitting or standing. In some instances, the observed change indeflection angle will be greater when the woman is standing. A womanwith strong pelvic floor muscles may be able to lift her pelvic floormuscles such that the device is oriented between 45° to 90° or more(e.g., nearly 90°) relative to the floor. If the woman has symptoms ofincontinence, she may exhibit hypermobility of her urethra, which can bereflected in a readout from the intravaginal device, which indicatesthat the pelvic musculature cannot fully hold and support the urethraand bladder in its correct place. In the event that a woman has extreme(e.g., stage IV) stress urinary incontinence and/or total POP, thesensor angle may be depressed towards 0° at rest. A physician may testthe woman's pelvic floor musculature by asking her to try to lift herpelvic floor, to perform a pelvic floor exercise, to cough or bear down,or to relax. In some cases of POP, when the woman attempts to bear down,the organs may deform the device in a caudal direction,

The data from the pelvic floor exercises may be uploaded automaticallyto an online database. The electronic device (e.g., a smartphone orcomputer) can also store a certain amount of this data. The applicationis user-friendly and can be configured to allow the patient to share herdata. The application can be a tool for the health care professional toprogram a specific exercise regimen for the patient or otherwisecommunicate with the patient. The application may privately communicatewith the patient by sending data, such as scores, charts, graphs, orreports, reminders, and encouragement to the patient via pushnotifications. The application can also allow patients to sendinformation to the database, responding to questionnaires and reportingcontinence, improvement, and/or problems.

The shape of the vagina can be determined using, e.g., data from, e.g.,the MEMS sensors in the device, which reflect the position of thepatient's pelvic floor in her body. The pelvic floor muscles lift thevaginal canal when a patient performs a PFL. The shape of the vaginafrom the data in the sensors can be used to monitor or diagnose a pelvicfloor disorder. For example, if the position of the patient's pelvicfloor descends, it can be useful to monitor the patient for possiblePOP. Monitoring the position of the patient's pelvic floor will help toprevent further damage and to correct and/or improve the current stateof a patient's pelvic floor, which may allow the patient to avoidsurgery or other more invasive options. The device may be used forprevention, rehabilitation, and treatment of urinary incontinence (urge,stress, and mixed), anal or fecal incontinence (gas, liquid, mucus,solid), POP, pelvic pain, sexual dysfunction, and postpartum health.

The device may show the patient and her health care professional themovement of the pelvic floor muscles as it is reflected by theconfiguration of the vagina in real time during training exercises.Using the biofeedback offered by the device, the patient alone, orassisted by her health care professional, can strengthen her pelvicfloor correctly. The data from the sensors allows for measuring andrecording the exercise data, giving the health care professional and/orthe patient the ability to track the patient's compliance, pelvic floorstrength, and improvement as a result of the patient's performance ofpelvic floor exercises.

The data may be captured as a score based an algorithm that measures theangles (location) of the sensor during PFL and may also include ameasure of the strength or endurance of the pelvic floor muscles. Thescore reflects the patient's pelvic floor exercises during her training(date and time). The device and application may provide point of caredata collection capabilities which may standardize care for pelvic floordisorders. The data created by the device may be transmitted to acentralized database creating a personal health record for the patient,providing care and measurable results.

This data can also provide predictive information that notifies apatient and their health care professional about the potential need forvarious treatment options to improve the patient's quality of life. Forexample, the changes observed in patients who have hypermobility aremarkedly different from patients that do not have hypermobility (e.g.,associated with stress urinary incontinence). By establishing a baselineon a patient using a device described herein and, e.g., a database ofinformation on the patient, one can monitor the patient's pelvic floordescent or damage in real-time or over a period of time. A devicedescribed herein can also be used to monitor a patient's improvementover time while using the device (e.g., to perform PFL that train andstrengthen the pelvic floor musculature). Therefore, the patient can betreated before the damage needs to be corrected through surgical means.

A device of the invention may also be used to characterize the healthstate or change in health state over time of a female patient. Forexample, the data generated by the device (e.g., the score) may becorrelated to various stages of POP (e.g., stage 0, I, II, III, and IV).A score of 0 may correspond to stage IV, 0-15 with stage III, 15-30 withstage II, 30-45 with stage I, and above 45 with stage 0. These scoresmay or may not be absolute scores, and they may be normalized for eachindividual patient. For example, a score range may be determinedempirically for each individual user. By tracking the score achievedduring certain exercises, the device can calculate a change ortransition from one health state to another (e.g., stage IV to stageIII, stage III to stage II, stage II to stage I, and stage I to stage0). For example, a severe prolapse patient at stage IV may initiate PFLsusing an intravaginal device of the invention. Over the course of a 3-6week treatment period, the patient performs a treatment regimen 1-10times per day, as described herein. The patient may start out generatingbaseline sensor data at rest. After the 3-6 week treatment period, thepatient may improve to stage II or III POP and may exhibit an upwardshift in sensor data during the PFL.

A device of the invention may also be used to monitor the long termhealth state of a female subject. For example, the device may beadministered as a routine test every time the female visits her generalpractitioner or OB/GYN specialist for a yearly checkup. The health stateof the female's pelvic floor can be monitored over time such that adeterioration in score may be used to predict that a pelvic floordisorder is oncoming. The device may be customized for each female(e.g., the circumference of the main body may be sized specifically forthe subject and/or the tether length may be selected based on the lengthof the subject's vaginal canal). The device may also have “smart”capabilities. For example, a woman with a pelvic floor disorder may wearthe device when performing routine daily activities. If she performs amovement that is detrimental to her pelvic floor health, the sensors maydetect the movement and the device may alert the female to halt theactivity.

Methods of Delivering Therapeutic Energy

Intravaginal device 100 may contain one or more energy transmitters(e.g., RF, laser, or electrical current stimulation). Energytransmitters 210 can be used to deliver therapeutic energy in the formof heat. RF transmitters can be used to provide nonablative radiofrequency in the form of thermal energy that treats vaginal disorders,such as skin laxity. By applying heat, the thermal damage stimulatescollagen production in deep layers of the skin and subcutaneous tissueto strengthen and fortify the collagen network in the vagina (e.g., theintroitus and tissues of the vaginal cavity, e.g., vaginal anterior,posterior and sidewalls). This may also trigger formation of newelastin. Furthermore, intravaginal device 100 may contain temperaturesensors 200 to track the heat generated by RF transmitters. Energytransmitters 210 (e.g., RF transmitters) may be positioned around mainbody 110 and/or along the length of tether 10. Exemplary therapeutic RFtransmitters and methods of treatment using such transmitters aredescribed, for example, in U.S. Publication Nos. US20170333705,US20130245728, US20150327926, US20160296278, US20170071651,US20180001103, US20160263389, US20160263388, US20160263387, andUS20150297908, and in Araujo et al., (An Bras Dermatol. 90(5): 707-721,2015) and Karcher et al., (Int. J. Wom. Derm. 2: 85-88, 2016), thedisclosures of which are each hereby incorporated by reference in theirentirety.

The device may be used for short or extended periods of time. Thedifferent RF transmitters distribute RF energy to different areas in thevagina (e.g., the introitus or areas within the vaginal cavity). RFtransmitters operate at one or more frequencies in the range of 1 kHz to100 MHz. The power level of RF transmitters may vary from 1 mW to 500 W,depending on physician recommendations and the duration of therapy.Temperature sensors 200 and microcontroller 900 automatically regulatethe frequency and power level applied by the device in order to regulatethe appropriate temperature for optimal patient comfort and therapeuticactivity. For example, RF transmitters can raise the temperature of thelocal tissue from 37° C. to 60° C. A cooling mechanism may be used toprevent the heat from reaching dangerous limits. Units of heat or energymay be transmitted as a unit per area of tissue (e.g., W/cm²). This isdescribed, for example, in Hsu et al. Obstet. Gynecol. 105 (5:1),1012-1017, 2005, Benedet et al. J. Reprod. Med. 37(9): 809-812, 1992,and in U.S. Publication No. US20180001103, the disclosures of which areeach hereby incorporated by reference in their entirety. For example,the one or more energy transmitters 210 (e.g., RF transmitters, lasers,electrical stimulators) may transmit energy (e.g., 1 mW-500 W, e.g., 100mW-300 W, e.g., 1-10 mW, e.g., 2 mW, 3 mW, 4 mW, 5 mW, 6 mW, 7 mW, 8 mW,9 mW, 10 mW, e.g., 10-100 mW, e.g., 20 mW, 30 mW, 40 mW, 50 mW, 60 mW,70 mW, 80 mW, 90 mW, 100 mW, e.g., 100-1000 mW, e.g., 200 mW, 300 mW,400 mW, 500 mW, 600 mW, 700 mW, 800 mW, 900 mW, 1 W, e.g., 1-10 W, e.g.,2 W, 3 W, 4 W, 5 W, 6 W, 7 W, 8 W, 9 W, 10 W, e.g., 10-100 W, e.g., 20W, 30 W, 40 W, 50 W, 60 W, 70 W, 80 W, 90 W, 100 W, e.g., 100-1000 W,e.g., 200 W, 300 W, 400 W, 500 W, 600 W, 700 W, 800 W, 900 W, or 1000 W)in units of energy per surface area of tissue (e.g., 1 mm² to 10 cm²,e.g., 1-10 mm², 10-100 mm², or 1-10 cm²) for an amount of time (e.g., 10seconds-30 minutes or more, e.g., 30 seconds, 1 minute, 10 minutes, 20minutes, or 30 minutes). The energy may also be transmitted to a certaindepth within the tissue (e.g., 0.1 mm-10 cm, e.g., 1 mm, 2 mm, 3 mm, 4mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 20 mm, 30 mm, 40 mm, 50 mm, 60mm, 70 mm, 80 mm, 90 mm, 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm,9 cm, and 10 cm).

Intravaginal device 100 can connect to a user interface, e.g., via asmartphone application by means of a USB port, Bluetooth Low Energy,Wi-Fi, or a similar wired or wireless technology. An application can beused by the patient or a physician to adjust the frequency, power level,or duration of treatment. Intravaginal device 100 may be battery poweredor connected to a power source, such as power box 810 (e.g., an externalbattery) or an AC outlet.

In order to effectively power energy transmitters (e.g., RFtransmitters) 210, intravaginal device 100 may be configured for usewith a large battery 800 or external power supply 810. Intravaginaldevice 100 may also be designed with tether 10 that is configured as aseparable tether with modular components. The top half of the device maybe configured as a long-term wearable component which contains the ringand part of the tether. Tether 10 can be connected to a separateshort-term device which may have additional RF transmitters to apply RFtherapy to the lower section of the vagina and/or the introitus. Battery800 may only power microcontroller 900, wireless radio 1300, andaccelerometers 200. A short-term device (e.g., modular and or separabletether) may be inserted into the vagina to connect to the long-device topower energy transmitters (e.g., RF transmitters) 210 and/or recharge abattery in battery 800. Alternatively, the short-term device may have awireless power transmitter and the long-term device may have a wirelesspower receiver. The long-term and short-term devices may have junctionsconfigured for connecting the two portions of the device. Theconnections may be, e.g., magnetic or other physical connections and mayprovide an electrical (e.g., Ohmic) connection. The magnetic connectionmay ease the connection of the separable pieces. Alternatively, aninterlocking, press fit, snap, or other mechanism may be used to connectthe modular tether (e.g., short term-device) to the long term wearabledevice.

When using the intravaginal device, the patient may also wish to use agrounding pad, which can be connected to the device and to the subjectin order to prevent the buildup of energy that could harm the patient.The use of a grounding pad is described in, e.g., Millheiser et al. (J.Sex Med. 7:3088-3095, 2010; incorporated herein by reference).

Methods of Optimizing Sensor Placement to Diagnose a Pelvic FloorDisorder with an Intravaginal Device of the Invention

The position of sensor(s) 200 of intravaginal device 110 may be locatedfor maximal signal change during a pelvic floor exercise and for maximalsignal-to-noise ratio. The device may contain one or more sensors 200(e.g., 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, or more) on main body 110 and/or tether 10. The fornix sensors aresensors that reside in the portions of the intravaginal device thatextend into the anterior and posterior fornices. Additional vaginalsensors reside, e.g., in the tether 10 caudal to the fornices. In oneembodiment, an intravaginal device as depicted in FIG. 2 may be used. Inthis embodiment, intravaginal device 100 has 12 sensors: 8 sensors intether 10 (S1-S8), and 5 sensors in main body 110 (S8-S12). Sensor S8 isshared by both main body 110 and tether 10. Once a device is designedwith optimally placed sensors, the device may be used to effectivelydiagnose or treat a pelvic floor disorder (e.g., POP).

As the intravaginal device has a known length, the vaginal length of asubject may be calculated by determining the length of the tether fromthe introitus of the vagina to the main body, when positioned within thevaginal fornices (FIG. 6). The intravaginal device may have a tetherthat extends beyond the introitus of the vagina or the tether may residecompletely inside the vagina.

Different vaginas may have different lengths and differentcharacteristic curvatures. Therefore, the physical characteristics ofintravaginal device 100 (e.g., length of tether 10, circumference ofmain body 110, number of sensors 200, and placement of sensors 200) maybe selected to optimize fit and function based on a particular vaginallength and curvature. These data derived from intravaginal device 100 ina patient may yield insight into the internal organ position and aid aphysician in diagnosing a pelvic floor disorder (e.g., POP). Forexample, sensors 200 of intravaginal device 100 within the vagina mayindicate that the cranial part of the vaginal canal is posteriorly andcaudally displaced, suggesting deformation from pelvic organ prolapse.

When the user performs a pelvic floor movement (e.g., Valsalva maneuver,PFL, sustained PFL, and repeated PFL), the angles (locations) of sensors200 change. For example, when using an intravaginal device with 12sensors, subjects, with a broad range of vaginal lengths, showed acaudal movement of the posterior fornix sensor during Valsalva maneuver(relative to the position of the posterior fornix during relaxation) anda cranial movement of the posterior fornix sensor during a PFL (again,relative to the position of the posterior fornix sensor duringrelaxation. In a subject with a short vagina (7.7 cm), caudal movementof the posterior fornix of 1.6 cm was seen during a Valsalva maneuverand cranial movement of the posterior fornix of 0.5 cm was seen during aPFL. In a subject with a long vagina (12.2 cm), 1.1 cm of caudalmovement was seen during Valsalva maneuver and 0.4 cm of cranialmovement was seen during PFL.

The comparison between the location of sensors on the tether 10, withinthe vaginal canal below the fornix, during various pelvic maneuvers,compared to the relaxed state, can help the physician to visualize thedeformation of the vaginal canal by extrinsic pelvic organs and in someinstances to diagnose a subject with a pelvic floor disorder (e.g., POPand/or hypermobility). Furthermore, because the main body 110 ofintravaginal device 100 surrounds, for example, a cervix, theintravaginal device is anchored in place, thereby providing referencepositions for visualization during relaxation and pelvic floor movementson a graphical user interface

Each sensor 200 may be used to measure a vaginal angle (0 _(V)) orfornix angle (θ_(F)) (FIGS. 3A-3D) based on the position and/ororientation of a sensor with respect to the virtual plane of theintroitus (“horizon”). Pairs of sensors 200 in main body 110, either inthe anterior fornix or within the lateral fornices, may be treated as anindividual node (FIG. 3A) of sensors. Therefore, the lateral fornixsensors A10 and A11 may be treated as a single node S9, while theanterior fornix sensors A9 and A12 may be treated as a single node S10(FIGS. 3B and 3D). The vaginal angle may be calculated by taking theaverage of the angle between two or more, or all, of nodes S1-S7 and thehorizon. The fornix angle may be calculated by taking the average of thetwo or more of the nodes S8-S10 relative to the horizon.

As the vagina and the fornix is not always straight, the vaginal andfornix angles may be calculated by multiple methods. For example, eV maybe calculated by averaging 2 or more sensors from S1-S8 relative to thehorizon, or by taking the best-fit line between S1 and S8 relative tothe horizon.

Thus, the change in the sensor position and orientation may bequantitatively analyzed using the metrics (e.g., vaginal angle andfornix angle) described above to evaluate pelvic floor movement.

The angles of each sensor may be tracked during pelvic floor movement.The angle of each individual sensor can be plotted on a time course(FIGS. 5A-5E, 6A-6C, 7-9, 10A-10B, and 11), and the time course may beannotated when certain pelvic floor exercises are performed (e.g.,Valsalva maneuver, lift, hold, and repeat). The change in the sensorangle may reflect a change in orientation of the intravaginal device atthat sensor location. Certain sensors may exhibit a stronger signal thanothers. For example, in FIGS. 9 and 11, sensors S4-S6 showed asignificant change in angle upon performing a hold. However, the othersensors did not exhibit a significant angular change. Additionally,sensors S7 and S8 showed an inverted angular response to the rest of thesensors as the angle decreased (instead of increased) from a relaxedposition.

This type of data may be collected empirically for any given subject(Example 13). As shown in FIG. 11, the data indicate that sensors S4-S6were located at a position to yield the greatest signal change duringpelvic floor movements and the largest signal to noise ratio relative tothe other sensors. As different female subjects have different vaginallengths and physical shapes, some variability may exist as to the signaloutput. For each individual subject, the specific sensor position andorientation may yield different information and exhibit different levelsof sensitivity. Thus, it may be possible to customize the size/length ofthe intravaginal device and the position of the sensors to optimize itfor use for a certain subject. These data can help guide optimalplacement of sensors in the most important positions of the intravaginaldevice to correctly correlate angular changes associated with specificpelvic floor disorders. In some instances, a sensor placed at a positionthat is approximately halfway between the introitus of the vagina andthe cervix or vaginal cuff produces a strong signal.

Methods of Detecting a Pelvic Floor Movement

The intravaginal device can be used to track pelvic floor movements(e.g., pelvic floor lift, pelvic floor relaxation, Valsalva maneuver,sustained pelvic floor lift, and serially repeated pelvic floor lift).Sensors S4-S6 (FIG. 3B) provide consistent signal to noise ratio,magnitude, and directionality (FIG. 11). Sensor S6 also provides astrong signal to noise ratio, but the directionality may vary indifferent subjects. One can use the data generated from one or more ofthese sensors in an algorithm that uses the sensor data to track theangle change over the course of daily activity in order to monitordifferent pelvic floor movements. The sensor data can be processed anddisplayed to the user or others via a graphical user interface. Forexample, a text message, email, alert via an application running on auser's peripheral device (e.g., smartphone) can be sent to a user orother subject. The microcontroller can store the computed data, e.g.,using a non-transitory storage medium. An algorithm can be used thatdefines one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more)parameters that constitute a composite score of one or more (e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, 10 or more) sensor angle measurements. An algorithmcan be used to track the change in angle of a single sensor or multiplesensors during a daily activity (e.g., during a pelvic floor movement).A first time derivative of the angle vs. time can be used to indicate apositive or negative change in angle with respect to time. A positiveangle change may indicate the start time or magnitude of a pelvic floormovement (e.g., lift) while a negative angle change may indicate the endtime or magnitude of decline (e.g., relaxation) of a pelvic floormovement. A second time derivative can be produced and used to indicatea local maximum or minimum that denotes when a movement is beginning orending (e.g., the rate of change of the angle with respect to time iszero). Additionally, the algorithm may be used to detect any pelvicfloor movements associated with daily activities that may be harmful toa user.

A user may insert intravaginal device 100 comprising a plurality of MEMSaccelerometers into her vagina and perform a series of pelvic floormovements (e.g., pelvic floor lift, pelvic floor relaxation, Valsalvamaneuver, sustained pelvic floor lift, and serially repeated pelvicfloor lift). Each MEMS accelerometer emits a signal corresponding to theposition and sensor angle relative to the horizon. The angle data fromeach sensor may be plotted as a function of time (FIG. 9). A compositescore may then be calculated from a summation of one or more of thesensor angles. A representative set of composite scores are shown inExample 14.

The algorithm may include, for example, calculating a moving average orfiltered composite score to reduce noise and minimize false positives.The filtered composite scores may be plotted versus time (FIG. 10A) anda derivative of this data may be plotted as a change in sensor angleversus time (FIG. 10B). When the change in sensor angle versus timeexceeds a predetermined threshold (e.g., 1°, 2°, 3°, 4°, 5°, 10°, 15°,20°, 25°, 30°, 35°, 40°, 45°, e.g., about 18°) it may be determined thata pelvic floor movement occurs. The predetermined threshold may bedetermined empirically from data collected from different subjects. Thestart of the pelvic floor lift may be determined at or about the instantthat the time derivative of the composite score of the filteredcomposite score exceeds the predetermined threshold. The peak values(e.g., Y_max) of the moving averages may indicate the magnitude of apelvic floor movement (e.g., a lift). The change in the composite scorefrom the start to the end of the movement may be defined as a Δ. Whenthe composite score of filtered average drops below a value of thedifference of the maximum score and the half maximum value of the Δ(e.g., Y drops below Y_max−0.5×ΔY) it may be determined that a pelvicfloor movement has ended. The coefficient before the Δ may be determinedempirically and may vary, e.g., from 0.1 to 1.0 (e.g., 0.1, 0.2, 0.3,0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0). The start and finish times ofthe movement may also be identified when the second derivative of thesensor angle with respect to time reaches zero (see, e.g., FIG. 10B).Any of the data or indicia may then be presented to the subject usingthe device or another individual, such as a health care provider.

Methods of Training an Intravaginal Device for Personalized Treatment

As certain sensors yield differential signal to noise ratios fordifferent subjects due to different internal anatomies and vaginallengths, the algorithm and composite scores can be optimized for eachuser. A weighted sum of the signal from each sensor may be used thatmore heavily weights the sensors that yield a strong signal (e.g., asensor signal with a higher signal to noise readout, such as sensorsS4-S6 (see FIG. 3B)) and less heavily weights the sensors that yield aweak signal (e.g., a sensor signal with a lower signal to noise readout,such as sensors S1-S3 and S7-S10 (see FIG. 3B)).

A user may insert intravaginal device 100 comprising a plurality of MEMSaccelerometers into her vagina and perform a series of pelvic floormovements (e.g., pelvic floor lift, pelvic floor relaxation, Valsalvamaneuver, sustained pelvic floor lift, and serially repeated pelvicfloor lift) under the guidance of a health care professional. The healthcare professional may teach the subject how to properly perform andexecute each of the pelvic floor exercises. The user may then performone or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) of each movementuntil the user executes the exercises properly.

As each MEMS accelerometer emits a signal corresponding to the positionand sensor angle relative to the horizon. The angle data from eachsensor is plotted as a function of time. The strength of the signal fromeach sensors is denoted by the change in angle (angle during pelvicfloor lift−angle during pelvic floor relaxation). This signal strengthmay be used to determine exactly which sensors provide the most robustsignal. For each user, a personalized set of parameters can becalculated to optimize a composite score and algorithm for a given user(see Example 15). The parameters may include, for example,multiplicative or additive coefficients for each sensor angle value. Anoptimized composite score may include a weighted average based on therelative signal strength of each sensor that changes depending on thesubject (FIG. 11). These algorithms and composite scores may be computedby the microcontroller, which can store the computed data, e.g., using anon-transitory storage medium.

The user may then perform the pelvic floor exercises on her own or mayuse the device to monitor pelvic floor movements during the course ofher daily activities. Based on the training regimen, the device cantrack the changes in sensor angles and alert the user when she isperforming the exercises correctly or incorrectly or when she engages inbeneficial pelvic floor movements (e.g., pelvic floor movements thatimprove a pelvic floor disorder or strengthen here pelvic floormuscles), or an adverse pelvic floor movement (e.g., one thatexacerbates a pelvic floor disorder or weakens. A processor that canconvert the sensor data into useable information can be included in theintravaginal device or in a peripheral device. Using a learning ortraining period can optimize the efficiency of the processor for a widerange of subjects and vaginal anatomies. The peripheral device ormicrocontroller may use artificial intelligence and machine learning tooptimize its algorithms for optimal detection of an occurrence of anevent (e.g., pelvic floor movement). Such artificial intelligencesystems are described, e.g., in U.S. Pat. Nos. 9,754,220 and 8,296,247,the disclosures of which are hereby incorporated by reference.

Methods of Treating a Pelvic Floor Disorder with an Intravaginal Deviceof the Invention Configured to Deliver a Pharmaceutical Agent

A female patient can use a device of the invention configured to deliverat least one (e.g., 1, 2, 3, 4, 5, or more) pharmaceutical agent inorder to treat, inhibit, or reduce the development of or progression ofa PFD, or other disease or condition, such as those described herein, ina similar fashion as described above. In some instances, an intravaginaldevice of the invention may be configured to deliver a pharmaceuticalagent by connecting a tether module that includes a delivery module orcomponent, inner core, reservoir, coating layer, and/or gel. In someinstances, an intravaginal device of the invention may be configured todeliver a pharmaceutical agent by connecting a sleeve that includes adelivery module or component, inner core, reservoir, coating layer,and/or gel. The device can be inserted into the vagina of the individualand a pharmaceutical agent may be delivered to the tissues of thevagina, e.g., before, after, or during the engagement of or relaxationof a PF muscle (e.g., the levator ani (e.g., the pubococcygeus,ileococcygeus, coccygeus, and puborectalis muscles) and the associatedconnective tissues, which span a spheric form from the pubic boneanteriorly to the sacrum posteriorly and to the adjoining bony structurejoining these two bones). The individual can also be monitored using theintravaginal device. Treatment with the device to deliver apharmaceutical agent may reduce the frequency of occurrence and/orseverity of at least one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more)symptom of a pelvic floor disorder. In particular, treatment includesmonitoring the performance of a PFL and/or PFR using the device over atreatment period during which time the pharmaceutical agent may bedelivered, e.g., constantly or periodically. The device may deliver apharmaceutical agent over a period of time ranging from about one weekto about three months (e.g., about 1-week, 2-weeks, 3-weeks, 4-weeks,2-months, or 3-months, e.g., about 7-21 days, 7-35 days, 7-49 days, 7-63days, 7-77 days, 7-91 days, or 7-105 days, e.g., about 2-8 weeks).

Methods of Combination Treatment

A female patient having, e.g., a PFD and/or another disease orcondition, such as those described herein, can use a device of theinvention configured to deliver at least one (e.g., 1, 2, 3, 4, 5, ormore) pharmaceutical agent in order to treat, inhibit, or reduce thedevelopment of or progression of the PFD and/or the disease or conditionof the vaginal tissue in a similar fashion as described above. Thedevice can be inserted into the vagina of the individual and apharmaceutical agent may be delivered to the tissues of the vagina,e.g., before, after, or during the engagement of or relaxation of a PFmuscle (e.g., the levator ani, e.g., the pubococcygeus, ileococcygeus,coccygeus, and puborectalis muscles) and the associated connectivetissues, which span a spheric form from the pubic bone anteriorly to thesacrum posteriorly and to the adjoining bony structure joining these twobones). The individual can also be monitored with the intravaginaldevice. Delivery of a pharmaceutical agent using the device may reducethe frequency of occurrence and/or severity of at least one (e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, 10, or more) symptom of the PFD and/or theadditional disease or condition. The device may be configured to delivera combination of pharmaceutical agent, e.g., a compatible combination ofpharmaceutical agents to treat both the PFD and the additional diseaseor condition of the user. In particular, treatment includes monitoringthe performance of a PFL and/or PFR using the device over a treatmentperiod during which time the pharmaceutical agent may be delivered,e.g., constantly or periodically. The device may deliver apharmaceutical agent over a period of time ranging from about one weekto about three months (e.g., about 1-week, 2-weeks, 3-weeks, 4-weeks,2-months, or 3-months, e.g., about 7-21 days, 7-35 days, 7-49 days, 7-63days, 7-77 days, 7-91 days, or 7-105 days, e.g., about 2-8 weeks).

Methods of Real-Time Monitoring (Live-Mode)

A female patient using an intravaginal device of the invention that isconfigured to provide real-time monitoring of the overall health statusof a user's urogenital system and/or pelvic floor (e.g., the musclefibers of the levator ani, e.g., the pubococcygeus, ileococcygeus,coccygeus, puborectalis muscles and associated connective tissues) maybe able to prevent or reduce the development and/or reoccurrence of aPFD and/or another disease or condition, such as those described herein.

An intravaginal device that is configured to monitor, e.g., musclemovement (e.g., a PFL and/or PFL, a muscle strain, a muscle stretch,and/or a muscle contraction), muscle quality, muscle strength, and/orpressure, may be able to provide feedback to a user and/or to a medicalpractitioner overseeing the user's treatment in real-time based on (i)daily activities that may reduce and/or improve the efficacy of a pelvicfloor muscle training program with an intravaginal device of theinvention; (ii) optimal times (e.g., in response to the performance of adaily activity) for the administration of a pharmaceutical agent; and/or(iii) alterations that may be made to a pelvic floor treatment program(e.g., increasing the frequency and/or intensity of a pelvic floortraining program that includes the performance of a series of PFLsand/or PFRs) to increase the efficacy of the treatment program. Inparticular, an intravaginal device of the invention may measure changes(e.g., increases and/or decreases) in, e.g., muscle movement (e.g., aPFL and/or PFL, a muscle strain, a muscle stretch, and/or a musclecontraction), muscle quality, muscle strength, and/or pressure of about1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%,80%, 90%, or more as compared to baseline values obtained, e.g., duringa calibration of the intravaginal device, or known in the art.

An intravaginal device that is configured to monitor, e.g., the level ofa toxin and/or hormone, pH, temperature, and/or humidity, can providefeedback to a user and/or to a medical practitioner overseeing theuser's treatment on (i) the onset and/or progression of a PFD and/oranother disease and/or condition affecting a user's urogenital systemand pelvic floor health; and (ii) the effectiveness of a treatmentprogram including the administration of pharmaceutical agent, asdescribed herein, by measuring changes in the level of a toxin, ahormone, pH, and/or humidity associated with a disease state. Inparticular, an intravaginal device of the invention can measure changes(e.g., increases and/or decreases) in, e.g., the level of a toxin and/orhormone, pH, temperature, and/or humidity of about 1%, 2%, 3%, 4%, 5%,6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more ascompared to baseline values obtained, e.g., during a calibration of theintravaginal device, or known in the art.

Methods of Use with an Additional Device

A female patient having, e.g., a PFD and/or another disease orcondition, such as those described herein, can use a device of theinvention in combination with an additional device that, in someinstances, is configured to deliver at least one (e.g., 1, 2, 3, 4, 5,or more) pharmaceutical agent in order to treat, inhibit, or reduce thedevelopment of or progression of the PFD and/or the disease or conditionof the vaginal tissue in a similar fashion as described above. However,in some instances, an additional device that may be used in combinationwith an intravaginal device of the invention is not configured todeliver a pharmaceutical agent.

In some instances, the additional device can be inserted into the vaginaof the individual and a pharmaceutical agent may be delivered to thetissues of the vagina, e.g., before, after, or during the use of anintravaginal device of the invention to measure the engagement orrelaxation of a PF muscle (e.g., the levator ani, e.g., thepubococcygeus, ileococcygeus, coccygeus, and puborectalis muscles, andthe associated connective tissues). The effectiveness of treatment withan additional device may also be monitored by an intravaginal device ofthe invention. For example, an intravaginal device of the inventionconfigured to detect a hormone and/or a toxin may be able to monitor theprogression the disease and/or condition being treated by the additionaldevice. Delivery of a pharmaceutical agent using an additional device incombination with an intravaginal device of the invention may reduce thefrequency of occurrence and/or severity of at least one (e.g., 1, 2, 3,4, 5, 6, 7, 8, 9, 10, or more) symptom of the PFD and/or the additionaldisease or condition. The additional device may be configured to delivera combination of pharmaceutical agents, e.g., a compatible combinationof pharmaceutical agents to treat both the PFD and/or the additionaldisease or condition of the user. In particular, treatment includesmonitoring the performance of a PFL and/or PFR using an intravaginaldevice of the invention over a treatment period with an additionaldevice during which time the pharmaceutical agent may be delivered,e.g., constantly or periodically. The additional device may deliver apharmaceutical agent one or more times over a period of time (e.g., astimed release or programmed release) ranging from about one week toabout three months (e.g., about 1-week, 2-weeks, 3-weeks, 4-weeks,2-months, or 3-months, e.g., about 7-21 days, 7-35 days, 7-49 days, 7-63days, 7-77 days, 7-91 days, or 7-105 days, e.g., about 2-8 weeks).Non-limiting examples of additional devices that may be used incombination with an intravaginal device of the invention include, butare not limited to, a vaginal pessary, a vaginal and/or analsuppository, a catheter, a bladder neck support device, a sponge, amenstrual device (e.g., a tampon or a menstrual cup), a vaginalstimulator (e.g., a device that contains one or more (e.g., 1, 2, 3, 4,5, 6, 7, 8, 9, or 10 electrodes; a device that contains a vibrator;and/or a device that contains a light emitting source), a vaginaldilator, and/or a device that contains a camera.

Methods for Detecting Additional Diseases or Conditions

The various embodiments of the intravaginal device as described hereinmay also be configured with one or more additional sensors to detect anadditional biometric parameter or disease or condition. For example, theintravaginal device may be configured with one or more accelerometers,gyroscopes, magnetometers, barometers, relative humidity sensors,bioimpedance sensors, thermometers, biopotential sensors, or opticalsensors.

The intravaginal device may be further configured with a biopotentialsensor or heartbeat waveform sensor to determine a user's heart rate.The heartbeat waveform sensor may be a photoplethysmography sensor or anECG sensor. Heart rate sensors may be used to track various heartconditions and alert a user, for example, if her heart rate increases ordecreases suddenly or deviates over time from an established baseline orcutoff level.

The intravaginal device may be further configured with an optical orbiopotential sensor that measures blood pressure. Blood pressure sensorsmay be used to track blood pressure conditions and alert a user, forexample, if her blood pressure increases or decreases suddenly. Suddenblood pressure change may be indicative of, for example, an oncomingstroke or heart attack.

The intravaginal device may be further configured with temperature, pH,or humidity sensors to detect the presence of, for example, a bacterialor fungal infection. An increase in internal temperature, humidity, orpH may be indicative of a fever or the body combatting an infection.

The intravaginal device may be further configured with gyroscope totrack movement, rotational, and balance disorders. If a subject exhibitsimproper movement or poor balance, the device may alert the user inorder to prevent, for example, a fall.

A processor that can convert the sensor data into useable informationcan be included in the intravaginal device or in a peripheral device.Using a learning or training period can optimize the efficiency of theprocessor for a wide range of subjects and vaginal anatomies. Theperipheral device or microcontroller may use artificial intelligence andmachine learning to optimize its algorithms for optimal detection of anoccurrence of an event (e.g., change in blood oxygen). Such artificialintelligence systems are described, e.g., in U.S. Pat. Nos. 9,754,220and 8,296,247, the disclosures of which are hereby incorporated byreference.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a description of how the compositions and methodsclaimed herein are performed, made, and evaluated, and are intended tobe purely exemplary for use in the compositions and methods of theinvention and are not intended to limit the scope of what the inventorsregard as their invention.

Example 1. Treatment of an Individual Having Urinary Incontinence (UI)with an Intravaginal Device

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to treat an individualhaving urinary incontinence (UI). The individual may have beenidentified as having a risk for developing UI (e.g., a subject who hasrecently experienced vaginal childbirth) or have been diagnosed ashaving UI by a medical practitioner. Alternatively, the individualexperiencing the symptoms of UI may self-identify as having a need totrain her pelvic floor (PF) muscles to reduce the frequency and/or theseverity of UI symptoms. The individual may obtain the device from amedical practitioner or from a retail outlet (e.g., a pharmacy).

The individual begins by inserting the intravaginal device into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff.

The individual will then perform a series of pelvic floor lifts (PFLs)to strengthen her pelvic floor muscles. The individual can perform aseries of PFLs for 15 seconds and then rests the muscles for 15 seconds,repeating the series for a total of 5 times over 2.5 minutes. The devicemeasures and collects results via sensors. The individual will performthis training program at least once a day, but preferably three timesper day for about one week to about three months. Over time, symptomsresolve. At the completion of the training program the device can beremoved.

Example 2. Treatment of an Individual Having Anal or Fecal Incontinencewith an Intravaginal Device

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to treat an individualhaving anal or fecal incontinence (FI). The individual may have beenidentified as having a risk for developing FI (e.g., a subject who hasrecently experienced vaginal childbirth) or have been diagnosed ashaving FI by a medical practitioner. Alternatively, the individualexperiencing the symptoms of UI may self-identify as having a need totrain her pelvic floor (PF) muscles to reduce the frequency and/or theseverity of UI symptoms. The individual may obtain the device from amedical practitioner or from a retail outlet (e.g., a pharmacy).

The individual begins by inserting the intravaginal device into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff. The patient may use the intravaginal device as outlined in FIG. 1.

The individual will then perform a series of pelvic floor lifts (PFLs)to strengthen her pelvic floor muscles. The individual can perform aseries of PFLs for 15 seconds and then rests the muscles for 15 seconds,repeating the series for a total of 5 times over 2.5 minutes. The devicemeasures and collects results via sensors. The individual will performthis training program at least once a day, but preferably three timesper day for about one week to about three months. Over time, symptomsresolve. At the completion of the training program the device can beremoved.

Example 3. Treatment of an Individual Having Sexual Dysfunction with anIntravaginal Device

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to treat a sexualdysfunction, such as caused by high pelvic floor muscle tone. Theindividual may have been diagnosed as having a sexual dysfunction by amedical practitioner. Alternatively, the individual experiencing thesymptoms of sexual dysfunction may self-identify as having a need totrain her pelvic floor (PF) muscles to reduce the frequency and/or theseverity of the symptoms of sexual dysfunction (e.g., painfulintercourse and vaginal laxity).

The individual begins by inserting the intravaginal device into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff. The patient may use the intravaginal device as described herein.

The individual will then use the device to relax the muscles of thepelvic floor. The individual can perform a series of PFR exercises. Theindividual will perform this training program at least once a day, butpreferably three times per day for about one week to about three months.Over time, symptoms resolve. At the completion of the training programthe device can be removed.

Example 4. Treatment of an Individual Having a Neurological Disease orInjury with an Intravaginal Device

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to treat a pelvic floordisorder (PFD) in an individual having a neurological condition, such asmultiple sclerosis (MS).

The individual begins by inserting the intravaginal device into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff. The patient may use the intravaginal device as described herein.

The individual will then perform a series of pelvic floor lifts (PFLs)to strengthen her pelvic floor muscles. The individual can perform aseries of PFLs for 15 seconds and then rests the muscles for 15 seconds,repeating the series for a total of 5 times over 2.5 minutes. The devicemeasures and collects results via sensors. The individual will performthis training program at least once a day, but preferably three timesper day for about one week to about three months. The individual mayalso use the device to track her experience of MS related PFD symptoms,such as the number of times she experiences urine or anal or fecalleakage per day. Over time, symptoms resolve. At the completion of thetraining program the device can be removed.

Example 5. Treatment of an Individual Having a Pelvic Floor Disorderwith an Intravaginal Device Containing an Electrical Impedance Myography(EIM) Sensor

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may contain an electrical impedancemyography (EIM) sensor, such as a SKULPT® sensor, and may be used totreat an individual having a pelvic floor disorder.

The individual begins by inserting the intravaginal device into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff. The patient may use the intravaginal device as described herein.

The individual will then perform a series of pelvic floor lifts (PFLs)to strengthen her pelvic floor muscles. The individual can perform aseries of PFLs for 15 seconds and then rests the muscles for 15 seconds,repeating the series for a total of 5 times over 2.5 minutes. The devicemeasures and collects results via the EIM sensors. Using the datacollected from the EIM sensors, the intravaginal device provides theindividual with a muscle quality score (e.g., a score reflective ofmuscle fiber density and organization). The individual will perform thistraining program at least once a day, but preferably three times per dayfor about one week to about three months. By using the intravaginaldevice, the individual may increase her muscle quality score. Over time,symptoms resolve. The device can be removed by the individual uponcompletion of the training program.

Example 6. Treatment of an Individual Having a Pelvic Floor Disorderwith an Intravaginal Device Containing a Light Detection and Ranging(LiDAR) Sensor

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) containing a light detection andranging (LiDAR) sensor may be used to treat an individual having apelvic floor disorder.

The individual begins by inserting the intravaginal device into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff. The patient may use the intravaginal device as described herein.

The individual will then perform a series of pelvic floor lifts (PFLs)to strengthen her pelvic floor muscles. The individual can perform aseries of PFLs for 15 seconds and then rests the muscles for 15 seconds,repeating the series for a total of 5 times over 2.5 minutes. The devicemeasures and collects results via the LiDAR sensors. Using the datacollected from the LiDAR sensors, the intravaginal device provides theindividual with three-dimensional (3D) model of her pelvic floor andvaginal tissues, which can be displayed to a user on a wirelesslyconnected electronic device via a user interface. A 3D model can begenerated at the start of treatment, e.g., a 3D reference model, andperiodically throughout, or after, the treatment program. Based on the3D models, e.g., a 3D model generated in substantially real-time, theuser may be guided to perform and or make corrections to her executionof pelvic floor lifts and/or relaxations. Movement data collected by theLiDAR sensors may also be used to monitor the performance of pelvicfloor lifts and/or relaxations and provide feedback to the user. Theindividual will perform this training program at least once a day, butpreferably three times per day for about one week to about three months.Over time, symptoms resolve. At the completion of the training program,the device can be removed.

Example 7. Treatment of an Individual Having Pelvic Organ Prolapse withan Intravaginal Device

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to treat an individualhaving pelvic organ prolapse (e.g., uterine prolapse). An individualdiagnosed as having a pelvic organ prolapse (e.g., uterine prolapse) bya medical practitioner may be prescribed an intravaginal device of theinvention configured to administer a dose of a pharmaceutical agent(s),such as a muscle stimulator. The individual may obtain the device fromthe medical practitioner or from a retail outlet (e.g., a pharmacy).

The individual begins treatment by inserting the intravaginal deviceinto the vagina (e.g., by using an insertion tool) and positioning thedevice proximal to the cervix or, for an individual with a hysterectomy,the vaginal cuff. The patient may use the intravaginal device asdescribed herein. The intravaginal device may be configured to releasethe muscle stimulator, e.g., during the performance of a pelvic floortraining exercise. Additionally, or alternatively, the intravaginaldevice may be configured to release an estrogen-compound (e.g.,estradiol) to restore the loss of estrogen to vaginal tissues that maybe weakened, for example, by age.

The individual will then perform a series of pelvic floor lifts (PFLs)to strengthen her pelvic floor muscles. The individual can perform aseries of PFLs for 15 seconds and then rest the muscles for 15 seconds,repeating the series for a total of 2-5 times over 30 seconds to 2.5minutes. The device measures and collects results via sensors, which candirect the release of the muscle stimulator, e.g., during theperformance of a PFL. The individual can perform this training programat least once a day, but preferably three times per day for about oneweek to about three months. Over time, symptoms resolve. If necessary,the intravaginal device (e.g., a refillable reservoir arranged withinthe intravaginal device), may be refilled to continue treatment with themuscle stimulator and/or the estrogen-related pharmaceutical agent. Atthe completion of the training program the device can be removed.

Example 8. Monitoring of an Individual's Pelvic Floor Health StatusDuring Daily Activities to Reduce Reoccurrence of a PFD

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to perform daily (e.g.,real-time) monitoring of the overall health status of a user'surogenital system and/or pelvic floor (e.g., the muscle fibers of thelevator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues) who haspreviously experienced a PFD (e.g., urinary incontinence) and who is atrisk of, but not currently experiencing, the reoccurrence of, e.g.,urinary incontinence symptoms. A medical practitioner may prescribe anintravaginal device of the invention as a prophylactic and diagnosticaid. The individual may obtain the device from the medical practitioneror from a retail outlet (e.g., a pharmacy). In some instances, forexample, when an individual already owns a base model of theintravaginal device (e.g., the main body of the intravaginal device) theindividual may need to obtain an expansion set (e.g., a tether or one ormore tether modules or separable tether portions) that can be used toadd the additional sensors and functionality required to perform dailymonitoring. Following the instructions provided with the expansion set,and available through the Application, a user may connect the tether orthe one or more tether modules or separable tether portions to the mainbody of the intravaginal device.

The individual begins treatment by inserting the intravaginal deviceinto the vagina (e.g., by using an insertion tool) and positioning thedevice proximal to the cervix or, for an individual with a hysterectomy,the vaginal cuff. The patient may use the Application to activate LiveMode to perform daily monitoring of the overall health status of theuser's urogenital system and/or pelvic floor. The Live Mode providesreal time visualization of the pelvic floor musculature that can be usedto train or educate the patient on the correct way to perform pelvicfloor exercises. For example, real time visualization during Live Modecan help a patient to understand how to activate muscles in the pelvicfloor that achieve “lift” rather than a “squeeze” without a liftingmovement. Activation of the pelvic floor muscles that achieve “lift,”which helps to strengthen the pelvic floor muscles and to improve thepelvic floor health of the patient, can be observed when the sensor(s)readout of the device (e.g., MEMS sensor(s) readout) shows movement ofthe device in an upward and frontward (e.g., caudal/anterior direction).The pelvic floor muscles shorten as they become stronger, whichtranslates into a lifting motion during PFMT. Using the sensors arrangedwith the main body and/or tether, the intravaginal device can collectdata as the user performs her daily activities and will provide feedbackto the user and/or to the medical practitioner overseeing her treatment.

If the intravaginal device detects a daily activity being performed thatmay weaken a user's pelvic floor muscles, the intravaginal device cannotify the individual and advise them to cease performance of thedetected activity. In some instances, the intravaginal device may adviseand/or schedule a reminder for the individual to perform a series ofpelvic floor lifts (PFLs) to strengthen her pelvic floor muscles inresponse to data collected during daily monitoring using Live Mode. Theindividual may then perform a series of PFLs for 15 seconds and thenrest the muscles for 15 seconds, repeating the series for a total of 2-5times over 30 seconds to 2.5 minutes. The individual can perform thistraining program when instructed to by the intravaginal device toprevent the reoccurrence of a PFD (e.g., urinary incontinence). Overtime, the feedback provided during the use of an intravaginal device mayhelp an individual to identify and reduce the performance of dailyactivities that may lead to the reoccurrence and/or development of aPFD, (e.g., urinary incontinence).

Example 9. Monitoring of an Individual's Hormone Levels to Detect Cancer

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to perform daily (e.g.,real-time) monitoring of the overall health status of a user'surogenital system and/or pelvic floor (e.g., the muscle fibers of thelevator ani, e.g., the pubococcygeus, ileococcygeus, coccygeus,puborectalis muscles and associated connective tissues) who haspreviously experienced a PFD (e.g., urinary incontinence) and who is atrisk of, but not currently experiencing, the reoccurrence of, e.g.,urinary incontinence symptoms. A medical practitioner may prescribe anintravaginal device of the invention that is configured to measurehormone levels to a patient at risk of developing uterine, cervical,and/or vaginal cancer (e.g., a patient who has previously been treatedfor a uterine or cervical cancer, but who is currently in remission).The individual may obtain the device from the medical practitioner orfrom a retail outlet (e.g., a pharmacy).

The individual begins treatment by inserting the intravaginal deviceinto the vagina (e.g., by using an insertion tool) and positioning thedevice proximal to the cervix or, for an individual with a hysterectomy,the vaginal cuff. The patient may use the Application to active LiveMode to perform daily monitoring of the overall health status of theuser's urogenital system and/or pelvic floor, and in particular tomeasure the level of hormones associated with the development ofuterine, cervical, and/or vaginal cancer. The intravaginal device cancollect data on hormone level(s) as the user performs her dailyactivities and can provide feedback to the user and/or to the medicalpractitioner overseeing her treatment.

If the intravaginal device detects a change (e.g., an increase and/or adecrease of about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%,40%, 50%, 60%, 70%, 80%, 90% or more) in the level of a hormones (e.g.,estrogen) that is associated with the onset, persistence, and/ormalignancy of a uterine, cervical, and/or vaginal cancer, theintravaginal device can notify the individual of the benefit ofscheduling an appointment with her medical practitioner to evaluate hercancer status. In some instances, the intravaginal device may advise themedical practitioner directly and/or schedule an appointment for thepatient so her cancer status can be evaluated,

Example 10. Monitoring of an Individual's Toxin Levels to Detect anInfection

An intravaginal device and/or system (e.g., an intravaginal devicesimilar to that shown in FIG. 1) may be used to perform daily monitoringof the overall health status of a user's urogenital system and/or pelvicfloor (e.g., the muscle fibers of the levator ani, e.g., thepubococcygeus, ileococcygeus, coccygeus, puborectalis muscles andassociated connective tissues) who is at risk of developing a fungalinfection, such as a yeast infection. A medical practitioner mayprescribe an intravaginal device of the invention as a diagnostic aid.The individual may obtain the device from the medical practitioner orfrom a retail outlet (e.g., a pharmacy).

The individual begins treatment by inserting the intravaginal deviceinto the vagina (e.g., by using an insertion tool) and positioning thedevice proximal to the cervix or, for an individual with a hysterectomy,the vaginal cuff. The patient may use the Application to active LiveMode to perform daily (e.g., real-time) monitoring of the overall healthstatus of the user's urogenital system and/or pelvic floor, and inparticular to monitor the level of toxins associated with the onset of afungal infection, e.g., a yeast infection. Using the sensors arrangedwith the main body and/or tether will then collect data as the userperforms her daily activities and can provide feedback to the userand/or to the medical practitioner overseeing her treatment.

If the intravaginal device detects a toxin level known to be associatedwith the onset of an infection, the intravaginal device can notify theindividual of the benefit of scheduling an appointment with her medicalpractitioner to evaluate her health status. In some instances, theintravaginal device may advise the patient to administer an appropriatepharmaceutical agent to treat the developing infection. In someinstances, the intravaginal device may notify the patient to connect atether or a tether module configured to administer the pharmaceuticalagent or recommend that the patient purchase, e.g., an over-the-counteranti-fungal agent that may be administered by the patient. For example,a patient may insert a suppository, e.g., a miconazole suppository, intoher vagina while continuing to use the intravaginal device to monitorthe toxin level throughout the treatment period. Over time, the feedbackprovided during the use of an intravaginal device may help an individualto identify and reduce the reoccurrence of fungal infections.

Example 11. Real-Time Data Output in Live Mode and Use with a SmartphoneApplication

An intravaginal device of the invention is connected to a transmitterbox that wirelessly (via Bluetooth) sends the positional data gatheredfrom the device sensors to a smartphone or computer that communicates tothe patient through a smartphone application. The shape of the vagina(data from the MEMS sensors in the device) reflects the position of thepatient's pelvic floor in her body. The data is captured as a scorebased on the angles of the sensors. The score is a measure of thestrength of the patient's pelvic floor muscles and increases as sheperforms her training over time. The data created by the device istransmitted to a centralized database creating a personal health recordfor the patient, providing care and measurable results.

This data can provides predictive information that notifies patients andhealth care professionals about the potential need for various treatmentoptions to improve the patient's quality of life. For example, thechanges observed in patients who have hypermobility are markedlydifferent from patients that do not have hypermobility (e.g., associatedwith stress urinary incontinence). By establishing a baseline on apatient using the device and the database of information on the patient,one could monitor the patient's pelvic floor descent or damage overtime. Therefore, the patient can be treated before the damage needs tobe corrected through surgical means.

A device of the invention is used to characterize the change in healthstate over time of a female patient. A female patient with stage IIIprolapse uses a device of the invention. After insertion of the devicefor the first time, the sensors read out that the device is positionedat a vaginal angle of ˜20°. When performing a PFL, the angle of thesensors moves toward 45°. She performs a series of exercises 1-10 timesa day (30 seconds-3 minutes per session) over the course of 3 weeks.After the 3 week treatment period, the woman is able to lift the devicesuch that the vaginal angle is 30°. This change in angle suggests thatthe woman has improved from stage III prolapse to stage II prolapse.

Example 12. Tracking Metrics of Sensor Readout as Patient ImprovesPelvic Muscle Strength

A patient with symptoms of urinary incontinence uses an intravaginaldevice for ˜2.5 minutes twice daily. After performing the exercises, theapplication computes an average weekly score, which increases from abaseline (screen) of 9 to a range of 44-52, reflecting the vaginal anglechanges during the lifting of the pelvic floor during exercises. Anincrease in score correlates with an increase in pelvic muscle strength.The application can also track endurance, which calculates the durationof time holding a lift during an exercise. After a 3 week exerciseregimen, the incontinence issue is assessed and, in many cases, would beresolved.

Example 13. Determining Optimal Sensor Positioning

An intravaginal device (see FIG. 2) was used to characterize specificsensor placement within the intravaginal device (e.g., within main body110 or tether 10) in ten subjects. The sensors in the main body werewithin the anterior fornix, lateral fornices and posterior fornix. Thesensors in the tether 10 were within the posterior fornix (shared by themain body) and along the vaginal canal caudal to the fornices. The mainbody contained 5 sensors, while the tether contained 8 sensors(including the one shared with the main body). The subjects had a rangeof vaginal lengths; these subjects were studied to determine if a subsetof the original 12 sensors consistently correlated with pelvic floormovement (e.g., PFL) when the subjects performed a variety of maneuversand demonstrated superior signal-to-noise characteristics. The sensorsin the fornix exhibited lower signal and provided less robustvisualization of pelvic floor movement. Of the sensors in the morecaudal portion of the vagina, sensors 4-6 exhibited a strong signalduring movement of the pelvic floor and favorable signal-to-noise ratio,even in female subjects having different vaginal lengths and physicalshapes. Thus, the placement of 2-3 sensors along the length of thetether of the intravaginal device, such that the sensors are positionedapproximately mid-way in the vaginal canal, yields robust signal output.Intravaginal devices with this placement of sensors (e.g.,accelerometers, such as MEMS sensors) can be used to diagnose abnormalpelvic floor movements and vaginal curvature associated with specificpelvic floor disorders.

Example 14. Using an Algorithm to Detect Pelvic Floor Movement

An intravaginal device comprising a plurality of MEMS accelerometers wasinserted into the vagina of a female subject and the subject was askedto perform a series of pelvic floor movements (e.g., pelvic floor lift,pelvic floor relaxation, Valsalva maneuver, sustained pelvic floor lift,and serially repeated pelvic floor lift). Sensor angle (relative to thehorizon) and position data from each MEMS accelerometer was collected(FIGS. 7-8). The angle data from each sensor was plotted as a functionof time (FIG. 9).

Two composite scores, Y1 and Y2, were calculated from the angles (A) ofsensors S5-S7:

Y1=A5+A6+0.6×A7

Y2=A5+A6−0.8×A7

A moving average of Y1 and Y2 (Y1_movmean and Y2_movmean) was calculatedfrom three consecutive samples of Y1 and Y2. The moving average filterwas used to reduce noise and minimize false positives. The filteredcomposite scores were plotted versus time (FIG. 10A) and a derivative ofthis data was plotted as a change in sensor angle versus time (FIG.10B). When the change in sensor angle versus time exceeded a thresholdof 18°, it was determined that a pelvic floor lift had occurred. Thisthreshold can be visualized by the slope of curve in FIG. 10A and thedashed line in FIG. 10B. The value of 18° was determined empiricallyfrom data from 10 different subjects. The start of the pelvic floor liftwas determined at the instant that the time derivative of the movingaverages of Y1 or Y2 exceeded this threshold. The peak values of themoving averages Y1 and Y2 were denoted Y1_max and Y2_max. The increasein the moving averages of Y1 and Y2 were denoted ΔY1=Y1_max−Y1_start andΔY2=Y2_max−Y2_start (FIG. 10A). These values indicated the magnitude ofthe pelvic floor lift. When the Y1_movmean dropped below a value ofY1_max−0.5×ΔY1 or the Y2_movmean dropped below a value ofY2_max−0.5×ΔY2, it was determined that the pelvic floor lift ended. Thestart and finish times were also correlated with the instant when thesecond derivative of the sensor angle versus time reached zero, as shownby the top and bottom of the spikes in FIG. 10B around 42 and 55seconds. The same data analysis was repeated for all pelvic floormovements (pelvic floor lift, pelvic floor relaxation, Valsalvamaneuver, sustained pelvic floor lift, and serially repeated pelvicfloor lift), as is denoted on the graphs.

Example 15. Detection of Pelvic Floor Movements During Daily Activitiesas a Measure of a Health State of a User

A user can insert an intravaginal device comprising a plurality of MEMSaccelerometers into her vagina and the device can detect pelvic floormovements (e.g., pelvic floor lift, pelvic floor relaxation, Valsalvamaneuver, sustained pelvic floor lift, and serially repeated pelvicfloor lift) during her daily activities. A processor in the device, orin a peripheral device, such as a smartphone or wearable device (e.g., awatch) can process the data to calculate the occurrence of a pelvicfloor event. Each MEMS accelerometer emits a signal corresponding to theposition and sensor angle relative to the horizon. The angle data fromeach sensor is plotted as a function of time. The strength of the signalfrom each sensors is denoted by the change in angle (angle during pelvicfloor lift−angle during pelvic floor relaxation). This signal strengthis used to determine which sensors provide the strongest signal. This isrepeated for 10 subjects (FIG. 11).

A parameter D_(MN) is defined as the angle “delta” for sensor M forpatient number N. S_(M) is defined as the angle for sensor M. Anoptimized composite score is defined as Y_(opt_N)=sum(1:10){D_(MN)×S_(M)}. Thus, the optimized composite score is a weightedaverage based on the relative signal strength of each sensor, whichchanges depending on the subject. In FIG. 11, the optimized compositescore for the first subject is given byY_(opt_1)=−1.1S₁−1.8S₂+1.2S₃+7.6S₄+6.9S₅−3.1S₆−10.2S₇−8.7S₈−5.1S₉−4.8S₁₀. The optimized composite score is calculated for the othersubjects (2-10) in a similar manner.

Example 16. Delivery of RF Energy for Therapeutic Applications

An intravaginal device and/or system (e.g., such as the one shown inFIG. 1) may contain one or more energy transmitters 210 (e.g., RF) andsensors 200 (e.g., temperature sensors) and may be used to treat anindividual having a vaginal or pelvic floor disorder. RF transmittersmay be positioned around main body 110 and along the length of tether10. The individual begins by inserting intravaginal device 100 into thevagina (e.g., by using an insertion tool) and positioning it proximal tothe cervix or, for an individual with a hysterectomy, to the vaginalcuff.

The intravaginal device may be used for short of extended periods oftime. RF transmitters distribute RF energy to different areas in thevagina. RF transmitters may operate at one or more frequencies in therange of 1 kHz to 50 MHz. The power level of the transmitters may varyfrom 10 mW to 300 W, depending on physician recommendations and theduration of therapy. Intravaginal device 100 may have sensors 200 thatare temperature sensors and microcontroller 900 to automaticallyregulate the frequency and power level applied to regulate theappropriate temperature for optimal patient comfort and therapeuticactivity. The device may connect to a peripheral device, such as a smartphone running an application capable of controlling the device, by meansof a USB port, Bluetooth Low Energy, Wi-Fi, or a similar wired orwireless technology. An application running on the peripheral device canbe used by the patient or a physician to adjust the frequency, powerlevel, and/or duration of treatment. The device may be battery poweredor may be connected to an external power source, e.g., power box 810(e.g., an external battery) or an AC outlet.

In order to power energy transmitters 210 (e.g., RF transmitters), thedevice can be designed with a modular tether that is separable into twocomponents. The top half of the device can remain inside the patient asa long-term wearable component 105, which contains ring 10 and part oftether 110. Tether 110 can be connected to a modular component of thetether, which can be configured as a separate short-term wearable device115 that may have additional energy transmitters 210, such as RFtransmitters, to apply RF therapy to the lower section of the vagina.Battery 800 may only power microcontroller 900, wireless radio 1300, andsensors 200, which may be accelerometers. Short term device 115 may comeinto physical contact with long-term device 105 to power transmitters210, such as RF energy transmitters and recharge battery 800, ifpresent. Alternatively, short-term device 115 may have a wireless powertransmitter and long-term device 105 may have a wireless power receiver.Long-term 105 and short-term 115 devices may have magnetic and/orelectrical (e.g., Ohmic) connections.

Example 17. Treatment of Skin Laxity

A patient with symptoms of urinary incontinence uses an intravaginaldevice having a ring and tether configuring with a radio frequencytransmitter. The patient inserts the intravaginal device and turns onthe RF transmitters at 5 W (10 V and 500 mA) for 20 minutes twice daily(5 minutes per area, 4 different areas). After turning on the radiofrequency emitter, a smartphone application computes a thermal index totrack how hot the intravaginal tissue becomes during treatment. Thethermal energy extends to 10 cm² area in contact with the transmittersand 1-10 mm below the surface of the vaginal tissue. Following each use,a short term modular tether component attached to an external powersource is attached the long term wearable device to recharge theinternal battery. After a 6 week treatment regimen, the incontinenceissue is assessed and resolved and the long-term intravaginal device isremoved.

OTHER EMBODIMENTS

All publications, patents, and patent applications mentioned in thisspecification are incorporated herein by reference to the same extent asif each independent publication or patent application was specificallyand individually indicated to be incorporated by reference.

While the invention has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodifications and this application is intended to cover any variations,uses, or adaptations for use in the compositions and methods of theinvention following, in general, the principles for use in thecompositions and methods of the invention and including such departuresfrom the present disclosure that come within known or customary practicewithin the art to which the invention pertains and may be applied to theessential features hereinbefore set forth, and follows in the scope ofthe claims. Other embodiments are within the claims.

1. A method of detecting a pelvic floor movement in a subject wearing an intravaginal device comprising one or more sensors comprising: a) obtaining positional data from the one or more sensors; b) processing the data from the one or more sensors to determine an occurrence of the pelvic floor movement; and c) employing the processed data to provide an alert presenting physiological data regarding the pelvic floor movement.
 2. A method of training an intravaginal device comprising one or more sensors comprising: a) obtaining positional data from the one or more sensors during performance of one or more pelvic floor movements by a subject wearing the intravaginal device; and b) processing the data from the one or more sensors to establish a baseline for identifying an occurrence of an event.
 3. The method of claim 1 or 2, wherein the subject performs more than one pelvic floor movement.
 4. The method of claim 3, wherein the subject performs a pelvic floor lift, a pelvic floor hold, a pelvic floor hold, and a Valsalva maneuver.
 5. The method of any one of claims 1-4, wherein the positional data includes one or both of sensor angle and time.
 6. The method of any one of claims 1-5, wherein processing the data comprises using an algorithm to calculate one or more composite scores.
 7. The method of claim 6, wherein the one or more composite scores are calculated from the sensor angles from the one or more sensors.
 8. The method of claim 7, wherein the composite score is a sum of the one or more sensor angles.
 9. The method of any one of claims 6-8, further comprising calculating a moving average of the composite score to filter noise.
 10. The method of any one of claims 6-9, further comprising calculating a change in sensor angle with respect to time.
 11. The method of claim 10, further comprising calculating a derivative of the change in sensor angle with respect to time.
 12. The method of claim 10 or 11, wherein when the change in sensor angle with respect to time exceeds a predetermined threshold, the pelvic floor movement is detected.
 13. The method of claim 12, wherein the predetermined threshold is 5°/sec, 10°/sec, 15°/sec, 20°/sec, 25°/sec, 30°/sec, or more.
 14. The method of any one of claims 9-13, wherein a peak of the moving average is defined as a maximum composite score.
 15. The method of claim 14, wherein when the moving average drops below a predetermined threshold, an end of the pelvic floor movement is detected.
 16. The method of claim 15, wherein the predetermined threshold is proportional to the maximum composite score.
 17. The method of any one of claims 11-16, wherein when the derivative of the change in sensor angle with respect to time is used to detect the start or finish of a pelvic floor movement.
 18. The method of claim 17, wherein the derivative of the change in sensor angle with respect to time is equal to zero.
 19. The method of any one of claims 1-18, wherein the intravaginal device comprises a plurality of sensors located along a length of the device.
 20. The method of claim 19, wherein the intravaginal device comprises a plurality of MEMS accelerometers located along the length of the device.
 21. The method of claim 19 or 20, further comprising optimizing the algorithm by measuring a change in sensor angle for each of the sensors, wherein the change in sensor angle is the difference between an angle during a pelvic floor lift and an angle during pelvic floor relaxation.
 22. The method of claim 21, further comprising calculating the composite score by using a weighted sum of each of the plurality of sensor angles.
 23. The method of any one of claims 1-22, wherein the method further comprises determining physiological indicia from one or more additional sensors.
 24. The method of claim 23, wherein the one or more additional sensors are selected from a gyroscope, a magnetometer, a barometers, a relative humidity sensor, a bioimpedance sensor, a thermometer, a biopotential sensor, a photoplethysmography sensor, and an optical sensor.
 25. The method of claim 23 or 24, wherein the physiological indicia are selected from steps, gait, activity, ballistocardiography, heart rate, heart rate volume, relative stroke volume, respiration rate, rotation, balance, pressure, relative humidity, body composition, temperature, pulse transit time, pulse oxygenation, and blood pressure.
 26. The method of any one of claims 23-25, wherein the physiological indicia are indicative of a disease or condition.
 27. The method of any one of claims 23-26, wherein the physiological indicia exceed or drop below a predetermined threshold.
 28. The method of claim 27, wherein the intravaginal device alerts the subject upon detection of a disease or condition.
 29. A peripheral device comprising a computer processing unit configured to receive data from one or more sensors in an intravaginal device, wherein the peripheral device is configured to process the data collected from the one or more sensors to establish a baseline for identifying an occurrence of a predetermined event.
 30. The peripheral device of claim 29, wherein the one or more sensors are MEMS accelerometers.
 31. The peripheral device of claim 29 or 30, wherein the processing step comprises using an algorithm that identifies a pelvic floor movement.
 32. The peripheral device of any one of claims 29-31, wherein the positional data includes one or both of sensor angle and time.
 33. The peripheral device of any one of claims 29-32, wherein processing the data comprises using an algorithm to calculate one or more composite scores.
 34. The peripheral device of claim 33, wherein the one or more composite scores are calculated from the sensor angles from the one or more sensors.
 35. The peripheral device of claim 34, wherein the composite score is a sum of the one or more sensor angles.
 36. The peripheral device of any one of claims 33-35, further comprising calculating a moving average of the composite score to filter noise.
 37. The peripheral device of any one of claims 33-36, further comprising calculating a change in sensor angle with respect to time.
 38. The peripheral device of claim 37, further comprising calculating a derivative of the change in sensor angle with respect to time.
 39. The peripheral device of claim 37 or 38, wherein when the change in sensor angle with respect to time exceeds a predetermined threshold, the pelvic floor movement is detected.
 40. The peripheral device of claim 39, wherein the predetermined threshold is 5°/sec, 10°/sec, 15°/sec, 20°/sec, 25°/sec, 30°/sec, or more.
 41. The peripheral device of any one of claims 36-40, wherein a peak of the moving average is defined as a maximum composite score.
 42. The peripheral device of claim 41, wherein when the moving average drops below a predetermined threshold, an end of the pelvic floor movement is detected.
 43. The peripheral device of claim 42, wherein the predetermined threshold is proportional to the maximum composite score.
 44. The peripheral device of any one of claims 38-43, wherein when the derivative of the change in sensor angle with respect to time is used to detect the start or finish of a pelvic floor movement.
 45. The peripheral device of claim 44, wherein the derivative of the change in sensor angle with respect to time is equal to zero.
 46. A system comprising the peripheral device of any one of claims 29-45 and the intravaginal device comprising one or more sensors.
 47. The system of claim 46, wherein the intravaginal device has a plurality of sensors located along a length of the device.
 48. The system of claim 46 or 47, wherein the sensors comprise one or more MEMS accelerometers.
 49. The system of one of claims 46-48, wherein the intravaginal device further comprises one or more additional sensors.
 50. The system of claim 49, wherein the one or more additional sensors are selected from a gyroscope, a magnetometer, a barometers, a relative humidity sensor, a bioimpedance sensor, a thermometer, a biopotential sensor, a photoplethysmography sensor, and an optical sensor.
 51. The system of claim 49 or 50, wherein the one or more additional sensors are configured to measure physiological indicia selected from steps, gait, activity, ballistocardiography, heart rate, heart rate volume, relative stroke volume, respiration rate, rotation, balance, pressure, relative humidity, body composition, temperature, pulse transit time, pulse oxygenation, and blood pressure.
 52. The system of claim 51, wherein the peripheral device is configured to establish a baseline measurement of physiological indicia selected from steps, gait, activity, ballistocardiography, heart rate, heart rate volume, relative stroke volume, respiration rate, rotation, balance, pressure, relative humidity, body composition, temperature, heart rate, heart rate volume, pulse transit time, blood pressure, pulse oxygenation, and blood pressure.
 53. The system of claim 52, wherein the peripheral device is configured to allow for transfer and analysis of the baseline measurements through one or more processes or mechanisms that enables operation of the intravaginal device to be personalized for a given user.
 54. The method of claim 1, wherein the positional data includes one or both of sensor angle and time.
 55. The method of claim 1, wherein processing the data comprises using an algorithm to calculate one or more composite scores.
 56. The method of claim 55, wherein the one or more composite scores are calculated from the sensor angles from the one or more sensors.
 57. The method of claim 56, wherein the composite score is a sum of the one or more sensor angles.
 58. The method of claim 55, further comprising calculating a moving average of the composite score to filter noise.
 59. The method of claim 55, further comprising calculating a change in sensor angle with respect to time.
 60. The method of claim 59, further comprising calculating a derivative of the change in sensor angle with respect to time.
 61. The method of claim 59, wherein when the change in sensor angle with respect to time exceeds a predetermined threshold, the pelvic floor movement is detected.
 62. The method of claim 61, wherein the predetermined threshold is 5°/sec, 10°/sec, 15°/sec, 20°/sec, 25°/sec, 30°/sec, or more.
 63. The method of claim 58, wherein a peak of the moving average is defined as a maximum composite score.
 64. The method of claim 63, wherein when the moving average drops below a predetermined threshold, an end of the pelvic floor movement is detected.
 65. The method of claim 64, wherein the predetermined threshold is proportional to the maximum composite score.
 66. The method of claim 60, wherein when the derivative of the change in sensor angle with respect to time is used to detect the start or finish of a pelvic floor movement.
 67. The method of claim 66, wherein the derivative of the change in sensor angle with respect to time is equal to zero.
 68. The method of claim 1, wherein the intravaginal device comprises a plurality of sensors located along a length of the device.
 69. The method of claim 68, wherein the intravaginal device comprises a plurality of MEMS accelerometers located along the length of the device.
 70. The method of claim 69, further comprising optimizing the algorithm by measuring a change in sensor angle for each of the sensors, wherein the change in sensor angle is the difference between an angle during a pelvic floor lift and an angle during pelvic floor relaxation.
 71. The method of claim 70, further comprising calculating the composite score by using a weighted sum of each of the plurality of sensor angles.
 72. The method of claim 1, wherein the method further comprises determining physiological indicia from one or more additional sensors.
 73. The method of claim 72, wherein the one or more additional sensors are selected from a gyroscope, a magnetometer, a barometers, a relative humidity sensor, a bioimpedance sensor, a thermometer, a biopotential sensor, a photoplethysmography sensor, and an optical sensor.
 74. The method of claim 72, wherein the physiological indicia are selected from steps, gait, activity, ballistocardiography, heart rate, heart rate volume, relative stroke volume, respiration rate, rotation, balance, pressure, relative humidity, body composition, temperature, pulse transit time, pulse oxygenation, and blood pressure.
 75. The method of claim 72, wherein the physiological indicia are indicative of a disease or condition.
 76. The method of claim 72, wherein the physiological indicia exceed or drop below a predetermined threshold.
 77. The method of claim 76, wherein the intravaginal device alerts the subject upon detection of a disease or condition.
 78. The peripheral device of claim 29, wherein the positional data includes one or both of sensor angle and time.
 79. The peripheral device of claim 29, wherein processing the data comprises using an algorithm to calculate one or more composite scores.
 80. The peripheral device of claim 79, wherein the one or more composite scores are calculated from the sensor angles from the one or more sensors.
 81. The peripheral device of claim 80, wherein the composite score is a sum of the one or more sensor angles.
 82. The peripheral device of claim 79, further comprising calculating a moving average of the composite score to filter noise.
 83. The peripheral device of claim 79, further comprising calculating a change in sensor angle with respect to time.
 84. The peripheral device of claim 83, further comprising calculating a derivative of the change in sensor angle with respect to time.
 85. The peripheral device of claim 83, wherein when the change in sensor angle with respect to time exceeds a predetermined threshold, the pelvic floor movement is detected.
 86. The peripheral device of claim 85, wherein the predetermined threshold is 5°/sec, 10°/sec, 15°/sec, 20°/sec, 25°/sec, 30°/sec, or more.
 87. The peripheral device of claim 82, wherein a peak of the moving average is defined as a maximum composite score.
 88. The peripheral device of claim 87, wherein when the moving average drops below a predetermined threshold, an end of the pelvic floor movement is detected.
 89. The peripheral device of claim 88, wherein the predetermined threshold is proportional to the maximum composite score.
 90. The peripheral device of claim 84, wherein when the derivative of the change in sensor angle with respect to time is used to detect the start or finish of a pelvic floor movement.
 91. The peripheral device of claim 90, wherein the derivative of the change in sensor angle with respect to time is equal to zero.
 92. The system of claim 46, wherein the intravaginal device further comprises one or more additional sensors.
 93. The system of claim 92, wherein the one or more additional sensors are selected from a gyroscope, a magnetometer, a barometers, a relative humidity sensor, a bioimpedance sensor, a thermometer, a biopotential sensor, a photoplethysmography sensor, and an optical sensor.
 94. The system of claim 92, wherein the one or more additional sensors are configured to measure physiological indicia selected from steps, gait, activity, ballistocardiography, heart rate, heart rate volume, relative stroke volume, respiration rate, rotation, balance, pressure, relative humidity, body composition, temperature, pulse transit time, pulse oxygenation, and blood pressure.
 95. The system of claim 94, wherein the peripheral device is configured to establish a baseline measurement of physiological indicia selected from steps, gait, activity, ballistocardiography, heart rate, heart rate volume, relative stroke volume, respiration rate, rotation, balance, pressure, relative humidity, body composition, temperature, heart rate, heart rate volume, pulse transit time, blood pressure, pulse oxygenation, and blood pressure.
 96. The system of claim 95, wherein the peripheral device is configured to allow for transfer and analysis of the baseline measurements through one or more processes or mechanisms that enables operation of the intravaginal device to be personalized for a given user. 